System for providing therapy to a patient

ABSTRACT

Systems and methods are described for adjusting the operation of implantable stimulation devices used to provide medical monitoring and treatment. Several hierarchical algorithms are described which operate according to conditionally obtaining a patient response to an alert signal. In one such strategy semi-automatic therapy adjustment occurs by automatically issuing patient alert messages when selected operations are to occur, and using a patient&#39;s response to the alert message that is provided within a selected time limit in order to contingently adjust therapy. Methods are also described for resolving conflicts which may occur when time information and sensed data information each indicate different patient states are occurring. Although treatment of neural and cardiac disorders is emphasized, the techniques can be applied to the monitoring and treatment of any medical disorder with an implanted device.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/877,897, filed Oct. 24, 2007, entitled “Methods and Systems forsemi-automatic adjustment of medical monitoring and treatment” basedupon U.S. Provisional Application 60/862,799 and is acontinuation-in-part of U.S. patent application U.S. application Ser.No. 11/309,605 filed Aug. 30, 2006, entitled “Medical treatment usingpatient states, patient alerts, and hierarchical algorithm”, saidapplication being based upon U.S. Provisional application No. 60/596,095filed, Aug. 31, 2005, entitled “Therapeutic treatment of medicaldisorders based on timing and state information” and U.S. Provisionalapplication No. 60/596,693 filed Oct. 13, 2005, entitled “Systems andMethods for Tissue Stimulation in Medical Treatment”.

FIELD

This invention is in the field of implantable monitoring and stimulationdevices, and more particularly to systems and methods of providing oradjusting treatment based upon patient preference, patient state values,and patient response values obtained from user input.

BACKGROUND

Medical stimulation devices that provide electrical and drug therapy arebeing used to treat a growing number of medical disorders. One type ofstimulation device is an implantable pulse generator (IPG), which may beprogrammable and can provide stimulation according to a set ofcustomized stimulation protocols. These protocols are tailored, andsometimes automatically and continuously adjusted, according to apatient′needs. An IPG is usually coupled to an electrical leadcontaining electrical contacts that provide stimulation to targettissue. When the IPG serves as a neurostimulator, the lead is typicallyimplanted to stimulate a particular region in the brain, vagus nerve, orspinal cord of a patient. The energy delivered through the leads'contacts creates electrical fields that modulates nearly tissue toproduce excitation, inhibition, or other modulation (e.g., promotingfiring at a particular frequency or according to a pattern) intended toprovide treatment for the disorder and relief from its symptoms. Anothertype of stimulation device is a drug delivery system in which a catheteris normally coupled to a pump that transmits drug from an implantedreservoir to targets that are in, or near, a treatment site.

Implantable stimulation devices can responsively provide treatment inaccordance with the patient's needs. For example, a sensor can obtainsensed data related to the activity or chemical level in adjacenttissue, and the sensed data can then be processed to extract features.These features are then evaluated in relation to treatment criteria, andtrigger stimulation treatment in response to defined medically relevantevents when these are detected. Sensed activity can also be used toautomatically adjust the stimulation protocol according to the featuresof the detected events or the patient's state. Sensed activity may alsobe used to responsively provide and adjust a stimulation signalaccording to features of the sensed signal using methods such as controllaws. For example, in the treatment of movement disorders, stimulationcan be automatically increased in response to sensed data which indicateincreased tremor activity using a proportional control law. U.S. Pat.Nos. 7,008,413, 6,463,328, 6,871,098, 6,832,114, 6,782,292, and5,716,377, and a wide array of other patents disclose various methods oftreating medical disorders (e.g., neurological, psychiatric, endocrine,metabolic, pain, cardiac, and movement disorders) by closed-loopstimulation treatment where adjustment and provision of stimulation canoccur automatically. In practice, fully automatic methods of providingstimulation may perform an intended to greater or lesser extents due toindividual differences of the patient and the variability of thepatient's daily routine. Many stimulation systems also allow patients toadjust treatment protocols using an external patient programmer thatcommunicates with the implanted device. Even when automatic programs areused, patients can invoke, adjust or cancel stimulation characteristicsset and used automatically by the device to improve therapy inaccordance with their preferences.

Implanted devices are normally powered by an implantable power sourcesuch as a battery that may be rechargeable or replaceable. In the caseof both rechargeable and replaceable batteries, power usage is animportant issue. Considerable benefit is obtained by decreasing powerconsumption and the need for replacement of electrical energy and, inthe case of drug delivery systems, medication. Many known systems andmethods provide therapy regardless of the time of day, or the activitylevel or state of the patient. During periods of sleep, phenomenaassociated with disorders (e.g. tremor and movement disorders) may beabsent, greatly diminished, or may simply not require treatment sincethese do not have any negative impact on the patient. Stimulatingidentically during sleep and awake states is not an efficient use ofresources and requires more frequent replenishment of the power or drugsupply. One class of stimulators does not have sensing capabilities andthus does not change stimulation based upon changes sensed in thepatient. Even when the stimulation system does not have a sensor,stimulation may be turned off and on by the patient in relation toperiods of sleep. Time information can be used to automatically inferpatient state and adjust stimulation accordingly.

The more recent generation of implantable stimulation devices isbecoming increasingly capable of automatically and responsivelyproviding stimulation according to the detection and quantification ofunwanted medical events such as seizures. This will increase batterylife and decrease habituation to stimulation since stimulation occurs asneeded in response to detected events rather than more or lesscontinuously. Even in stimulators that have sensing capability, patientstate may often be ignored. More specifically, these systems provide foradjusting the stimulation protocol in response to sensed data (e.g.,detection and quantification of medically relevant events), regardlessof certain other factors that should also be considered such as patientstate (e.g. the arousal level of a patient which is not related tomedically relevant events). Unless the patient manually turns off thestimulator, stimulation often occurs regardless of whether the patientis awake or asleep.

Aside from unnecessarily depleting resources, a second and possibly moreimportant factor is that, in some disorders, providing continuousstimulation generally increases the risk that a patient will developtolerance, and subsequently need increased stimulation to achieve thesame level of treatment benefit. In order to mitigate these twoconcerns, patients will often be instructed to manually turn off astimulation device, such as a neurostimulator, at night or whilesleeping. However, patients may occasionally or even regularly forget tofollow these instructions and, even when they do remember, the return ofsymptoms prior to falling asleep may inhibit the patient fromsubsequently achieving sleep. The use of stimulators, whichautomatically adjust the stimulation treatment according to thepatient's daily routines (e.g., as can be indicated by pre-defined timesor sensed data), will improve treatment in these cases.

Three known approaches have provided methods of automatically alteringtreatment according to time information or sensed data. In U.S. Pat. No.6,463,328 to John (“the '328 patent”), multiple stimulation leads ordrugs may be used to treat neurological disorders. The stimulationprotocol that governs therapy provided at each stimulation conduit canbe governed by “conditional criteria”. As described in the '328 patent.“Conditional criteria are additional parameters such as time since laststimulation, time of day, etc., and can be designed so that stimulationoccurs only at certain stimulators under specified conditions”Accordingly, stimulation occurs only during certain times, for example,while the patient is normally awake.

It is instructive to note that the '328 patent also describes that evenin cases of coma “stimulation can be set to reinforce present oremerging circadian cycles and not to occur during an inappropriatechrono-biological state, such as periods which might suggest sleep orless active states”. In this patent, if sensed data indicate that thepatient is sleeping, or if conditional criteria indicate thatstimulation should not occur during a specific time of day (for example,when the patient is likely to be sleeping) then stimulation does notoccur. In the '328 patent the changes occur automatically according tosensed data or time information. The patient is not alerted to, orquestioned about, the changes made by the device, nor are adjustmentsother than “on” vs. “off” specifically addressed.

More recently, U.S. Pat. No. 6,923,784 to Stein (“the '784 patent”)describes “automatically shutting off the electrical stimulation or drugdelivery during periods when the patient does not require treatmenttherapy.” Stimulation is halted when sleep is detected or during timeswhen sleep is likely. While much of the '784 patent appears to describemethods already taught and claimed in the '328 patent, two features areworth noting. Conflicts between sensor readings and the time of daycriteria are resolved automatically and without patient intervention. Inone example, if the time of day indicates that stimulation should behalted because the patient is likely sleeping, but information from asensor indicates that the patient is still clearly awake (usingstringent criteria), then stimulation continues rather than beinghalted. Moreover, additional measures (e.g., heart and respirationrates, eye activity) are sensed and evaluated in order to determine if apatient is sleeping or awake. Only complete cessation of stimulation isdescribed; halting the sensing and evaluation protocols is notmentioned.

U.S. application Publication No. 20040215286 to Stypulkowski (“the '286application”) controls therapy by means of a base stimulation programand one or more patient condition algorithms. The base stimulationprogram is modified according to the patient condition algorithms togenerate multiple neurostimulation programs. The base program serves asa starting point for the generation of multiple neurostimulationprograms tailored to patient activities. The patient conditionalgorithms may correspond to different patient conditions such as awakeand sleeping or patient activities, such as sitting, and exercising.This strategy constrains the range of the possible parameter values (andpermutations) used to provide stimulation, by using a base program as astarting point for subsequent modifications. Further, the patientcondition algorithms only relate to adjusting characteristics ofstimulation such as “pulse amplitude and pulse width”. No mention ismade of altering any sensing or evaluation routines in order to beresponsive to different types of medical events, or in order to saveenergy, while the patient is in one state or another. The stimulationprogram is selected in one of two manners, either manually basedentirely on input from the patient or automatically based on a sensedcondition.

Two additional publications should also be noted; these provide methodsby which treatments of implantable stimulation devices are adjusted inconjunction with patient input. In U.S. application Publication No.20040199215 to Lee et al. (“the '215 application”), a clinicianprogrammer may maintain a session log for the patient that includes alisting of programs delivered to the patient and rating information,provided by a clinician and the patient, for the listed programs. Thesubsequent selection of therapy programs is improved since highly ratedprograms can be selected with priority. In U.S. Pat. No. 6,986,347 toHickle (“the '347 patent”), an apparatus and method are described forproviding a patient relief from pain and anxiety associated with medicalor surgical procedures. In this case a computer system is used todispense medication. The patient may make a request for an increase ordecrease of drug therapy, and the physician approves or denies therequested change.

It would be advantageous for systems and methods to address certainshortcomings in the known approaches, and to provide adaptive therapyprograms based on calculated patient states and expressed preferences,computed from time information, sensed information, and patient input.The current invention offers a number of advantages that address theshortcomings of the prior art and provides other novel features as willbe made clear.

SUMMARY

Systems and methods are described for adjusting treatment, duringdifferent periods, as the treatment needs of the patient vary. In oneembodiment, the stimulation system has a clock which provides timeinformation which is used while determining patient state. The systemmay automatically revert to a sleeping protocol at a time when thepatient is usually sleeping and revert to a waking protocol near a timewhen a patient normally awakes. The system may also use sensed data todetermine the state of a patient. Patient state is used to make a changein the treatment such as adjusting the sensing, stimulation, andevaluation protocols. Unlike known systems, a system according to theinvention may automatically alert the patient to a proposed adjustmentand wait a selected duration for approval from the patient for thisadjustment prior to making the proposed adjustment. Patient alert rulesare provided which allow the device to continue to operate according tothe response of the patient or even when the patient does not respond.These rules can be implemented by a therapy control program whichautomatically alerts the patient to a proposed adjustment, obtains inputfrom the patient with respect to the proposed operation, and operatesthe device, according to these rules, while waiting for this input. Thesystem also can include a treatment program which selects which of twoor more protocols to use based upon patient state information and canadjust particular parameters of a protocol according to thisinformation. The invention provides a number of methods that utilize,and systems which implement, treatment which is adjusted based changesin patient state.

Four advantages treatment features are primarily realized by the methodsand systems of the present invention. A first feature automaticallyalerts patients by providing notice before adjusting or providingtherapy, and rules are provided for operating according to patient'sresponse to the alert. A second feature adjusts the evaluation andsensing protocols based upon patient state. A third feature implementshierarchical treatment methods wherein operations that occur at higherstages are contingent upon operations at lower stages. A fourth featuredynamically changes priority rules, based upon specific times or events.In various embodiments, the invention can be implemented fully orpartially within an implanted treatment device, a patient programmer, ora separate device which communicates with either of these (e.g., acomputer that may, or may not, be connected to other computers over theinternet; or, an implanted device that communicates with one or moreimplanted stimulation devices). A system according to the invention canbe programmed to switch among protocols primarily automatically, orsemi-automatically, or both (concurrently or alternatively, dependingupon events). The invention can be combined with other known methods. Aswill be described in further detail below, these features can be usedeither separately or in combination to provide a multitude of advantagesto the patient. A number of variations and advantages will be describedfor each feature.

Accordingly, an embodiment of the invention provides a system and methodof providing therapy, wherein adjusting a treatment protocol includesdetermining that an adjustment in the treatment protocol should occur,alerting a patient to a proposed operation by providing an alert signal,and said adjustment in the treatment protocol occurring, or notoccurring, only after a “response condition” is evaluated as true. Aresponse condition may be evaluated as true due to an “accept” or“reject” patient response from the patient, an expiration of a timelimit without a response (i.e., “no response”), a presence or absence ofa defined sensed condition having priority, or any of numerous otherpossibilities. Illustrative patient response rules which guide theoperation of the device while awaiting a response, until the responsecondition terminates, will be described in detail below.

In an embodiment of the current invention, a method of adjusting atreatment protocol includes determining that an adjustment should occur,alerting a patient to a proposed adjustment in the treatment protocol byproviding an alert signal, and performing the proposed operation only ifthe patient approves the adjustment or a time limit is reached.

In an embodiment of the current invention, a method of adjustingtreatment operations includes determines that an alert event hasoccurred, notifying a patient with an alert signal, adjusting operationaccording to the patient's input response. In addition to approving orrejecting the proposed operation, the patient may also delay theproposed adjustment, request a reminder alert, modify the suggestedadjustment, or choose between 2 or more proposed adjustments. The alertsignal can also include a request to answer 1 or more questions, theanswers to which can be used to semi-automatically modify treatment.

According to an embodiment of the invention there are provided methodsfor automatically sending alerts to the patient in order to accomplishat least one of the following to resolve conflicts between time andsensor information (or to one piece of information out of several withineach category); to resolve conflicts between two or more types of sensorinformation; to assign priority to time or sensor information; to selecta priority rules; to alert the patient about a proposed adjustment; torequest that a patient set an order of priority rules; and, to provide aresponse that assists with the evaluation of sensed data or otheroperation related to provision of therapy.

According to an embodiment of the invention, patient alert rulesdetermine what type of alerts signals are sent to the patient accordingto different alert events, how long to wait for a reply from thepatient, what to do while waiting, what to do in the case of multiplealert events occurring over a short period (e.g., according to thehistory of alert events, or in the case of overlapping alerts), and whatto do in the case where the patient does not respond to an alert messagehaving waited the predetermined amount of time. A device according tothe invention may be operative to send an alert signal prior toproviding at least one type of selected therapy, such as stimulationover a specified amount or duration, and the stimulation may be providedaccording to a change in patient state or in response to a detectedmedical event.

According to an embodiment of the invention, pre-emptive stimulationstrategies may be used to automatically send alert signals related toanticipated future events, even when no medical events requiringtreatment have been detected. It will be recognized that treatment maybe adjusted in a system according to the invention based on ananticipated patient state rather than the patient's current state.

According to an embodiment of the invention, various combinations ofautomatic, manual, and semi-automatic types of methods may be used in asystem according to the present invention to provide treatment, where amethod type can be set to occur accordingly to user preference atdifferent times, concurrently with a different method type, in responseto various patient states and the detection of different events, andaccording to threshold criteria.

Moreover, as well as adjusting control laws, sensing and evaluationprotocols may be adjusted based upon patient state information, torealize control laws, and alert messages may be sent automatically priorto such adjustments being implemented.

Accordingly, then, an embodiment of the invention provides adjustment ofthe sensing and evaluation protocols at different times and underdifferent conditions. Under the adjusted protocols, different types ofevents can selectively lead to stimulation treatment, wherein one typeof adjustment requires events to be of a larger magnitude (i.e., than isused during other states) during a patient state for which the treatmenttherapy is less needed by a patient. For example, a sleeping protocolmay be enabled, in which stimulation only occurs in response to eventswhich are detected using a second threshold which is different from(e.g., larger than) a first threshold that used when the patient isawake.

In an embodiment of the invention, sensed data are evaluated based uponan evaluation protocol that is adjusted continually, periodically, oroccasionally based, at least partially, upon the patient state. Further,sensing and evaluation protocols can be altered based upon patient statevalues and the stimulation protocols are then adjusted contingent uponthe selected sensing or evaluation protocols. In an embodiment of theinvention, this pairing of sensing, evaluation, and stimulationprotocols is defined using S-EVA-S set rules which can be defined in andimplemented by the treatment program.

An embodiment of the invention provides varying methods of treatment,wherein conflicting data are resolved automatically, using dynamicpriority rules or by providing notice to the patient and actingdifferently depending on the patient's response, if any.

An embodiment of the invention provides treatment using multi-levelsensing and evaluation protocols, and hierarchical algorithms, in whicha secondary protocol is enabled only if a first level condition issatisfied. More complex or comprehensive processing and evaluation ofsensed data may be configured to occur only if less complex operationshave met a level criterion, such as the detection of a certain clinicalevent. For example, sending data to an external programmer for furtheranalysis or sensing from a second set of sensors can occur in higherlevel protocols using a multi-level algorithm. In an analogous manner,treatment parameters and treatment protocols may also be variedaccording to similar hierarchical analysis of conditions, detections,and patient inputs. Patient input can be used to meet a level criterion.

An embodiment of the invention provides treatment which adjusts by aclinically relevant and significant amount at least one therapyparameter, such as its duration, location, amplitude of stimulation, ordosage during a patient state for which the treatment therapy is neededmore or less by a patient. Alternatively, different treatment protocolsmay be selected, at least one of which adjusts by a clinically relevantand significant amount some metric of therapy intensity. For example, asleeping protocol may decrease stimulation during sleep, stimulateintermittently or irregularly rather than continuously, or otherwisemodify the type, location, or dose of electrical or pharmaceuticalstimulation. The adjustment can cause the amount of stimulation tochange by a significant amount which is, for example, at least 30%.

An embodiment of the invention provides an implantable stimulationdevice that contains protocol sets of at least tow or more sensing,evaluation, and stimulation protocols that may be adjusted based uponpatient state information.

An embodiment of the invention includes an implanted programmer-timercapable of estimating or calculating patient states relevant to theprovision of therapy, wherein the implanted programmer-timercommunicates with a generic implanted stimulation device either directlyor via an external patient programmer to effect changes in treatmentaccording to the patient state.

An embodiment of the invention provides a method wherein therapy isadjusted for a network of two or more implanted stimulator devices. Forexample, bilateral stimulation can be applied in an alternating mannerusing a diurnal cycle. Hence, the methods and systems of the currentinvention can be implemented as an independent device which cancommunicate with an implantable stimulator, or a network of stimulators,to deliver treatment according to the principles described herein inorder to provide improved therapy to the patient.

The current invention offers a number of objects and advantages thataddress certain shortcomings noted in known approaches, and alsoprovides other improvements as will be made clear in the followingdescription of the inventive methods and systems and the associatedfigures and claims. The current invention implements the foregoingaspects and features, alone or in various advantageous combinations, inorder to provide improved therapy to the patient. Especially whenimplemented within fully automatic, closed-loop devices, the addition ofthese features will provide increased therapeutic benefit a portion ofthe time.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention and its advantages, thereis provided a detailed description and accompanying drawings ofembodiments which are presently preferred, it being understood that theinvention is not intended to be limited to the precise arrangements andinstruments shown, and wherein:

FIG. 1A shows an embodiment of the invention in which an electricalstimulator and a drug delivering stimulator are implanted to provideneurostimulation to a patient's brain;

FIG. 1B shows an alternative embodiment of the system of FIG. 1A inwhich some sensors and stimulators are physically distinct and in whicha timer-programmer is used;

FIG. 2A is a schematic representation illustrating the components of astimulator according to an embodiment of the present invention;

FIG. 2B is a schematic representation of the components of a stimulatoraccording to an embodiment of the present invention, wherein thestimulator includes a sensing subsystem for sensing data from thepatient;

FIG. 3A is a schematic representation of an implanted programmer-timeraccording to an embodiment of the invention, wherein theprogrammer-timer adjusts the operation of a generic stimulator;

FIG. 3B is a schematic representation of the components of aprogrammer-timer according to an embodiment of the present invention,wherein the programmer-timer utilizes information obtained from asensing subsystem of a generic stimulator;

FIG. 4 is a schematic representation of the modules of a controlsubsystem according to an embodiment of the invention;

FIG. 5 is a schematic block representation of a method for selectingprotocols in accordance with an embodiment of the present invention,wherein patient state information is used to select protocols fortreatment;

FIG. 6A is a schematic block diagram of another method in accordancewith an embodiment of the present invention, wherein alert signals areautomatically provided to the patient and alert rules are used tosemi-automatically guide treatment;

FIG. 6B is a schematic block diagram of another method in accordancewith an embodiment of the present invention, wherein alert messages areautomatically sent to the patient, and patient responses are used tosemi-automatically guide treatment;

FIG. 7 is a schematic block diagram of a method in accordance with anembodiment of the present invention, wherein changes in a patient'sstate adjust treatment according to patient state rules;

FIG. 8 is a schematic block diagram, of another method in accordancewith an embodiment of the present invention, wherein classification of apatient's state automatically adjusts treatment;

FIG. 9 shows a schematic representation of a serially-implementedhierarchical method for evaluating sensed data and providing therapyusing level criteria;

FIG. 10A shows a schematic representation of a general hierarchicalmethod for applying two treatment protocols as indicated by levelcriteria;

FIG. 10B shows a schematic representation of a hierarchical method whereat least one of a higher-level set of treatment protocols is selectedusing multiple level criteria;

FIG. 11A is an exemplary timeline illustrating patient-directedselective therapy activation according to an embodiment of theinvention;

FIG. 11B is an exemplary is an exemplary timeline illustrating therapyprogram modification according to condition changes, detected events,and patient inputs according to the invention; and,

FIG. 12 is a schematic representation illustrating the external patientprogrammer according to an embodiment of the present invention.

DETAILED DESCRIPTION

The definitions of terms written in this specification shall beconsistent with the context in which the terms appear and the ordinarybroad meaning of such terms as would be understood by practitioners ofordinary skill in the arts relevant to the invention; withstanding that,exemplary definitions (which are illustrative but shall not beconsidered limiting) are included at the end of the specification.

FIG. 1A shows a patient 8 implanted with a neurostimulation systemincluding a stimulator device 10 a. The stimulator 10 a may be implantedin the chest area, or it may be located within the skull, in the brain,or in any other location within the patient. Alternatively, thestimulator 10 a may be partially external. At least one stimulationconduit 12 a is provided which is positioned to stimulate a specificsite in a patient's brain. In the figure, the stimulation conduit 12 acomprises two leads 14 a, 14 b that are implanted into different areasof the brain. The two leads 14 a, 14 b can each have one or moreelectrical contacts 15. A selected stimulation protocol can specificallyprovide stimulation at one or more of the electrical contacts 15 of theleads 14 a, 14 b. When used to treat a central nervous system (CNS)disorder, the stimulation conduit 12 a may be realized as any leaddesigned for stimulation of the spinal cord, cranial nerves, vagusnerve, or other tissue of the patient that is part of or can modulatethe CNS. As is also shown in FIG. 1A, the stimulation conduit 12 b canbe realized as at least one catheter, which provides drug delivery to anoutput 16 at a desired tissue location from a drug pump stimulationsystem 10 b. When the stimulator 10 b is used to treat variousdisorders, the stimulator conduit 12 b may be a catheter designed todeliver one or more drugs which are able to modulate tissues, organs,and biological processes related to the disorder, such as intrathecaldrug delivery of morphine in the treatment of pain. The wall of thecatheter can contain electrical communication means that have a proximalsection which connects to the stimulation system 22 (FIG. 2) via routingcircuitry in the control subsystem 20 and a distal end which terminatesat a contact 15 b. The contact 15 b can provide both electricalstimulation and sensing. A separate contact 15 c is locatedperipherally, and is used to sense electromyographic (EMG) activity in alimb. As is well known, when a drug infusion system 10 b is used, thiscan include a pump and at least one reservoir for storing at least onedrug to be delivered via at least one catheter having at least onelumen. Exemplary drug infusion systems capable of employing the presentinvention are disclosed in U.S. Pat. application Pub. Nos. 20060173406,2004220552, 20040153029; 20040127942; 20040059315, 20040193255;2005154370; and 2003199813; PCT Publication W02005-007223; and U.S. Pat.Nos. 7,025,743; 6,902,544; 6,999,854; 6,269,340; and 5,975,085. Theinvention may be implemented within a system similar to the Paradigm™drug pump for providing insulin in the treatment of diabetes. Theinvention can also be implemented within various types of emergingchip-based drug delivery systems, some of which may not utilize acatheter.

Treatment can also include magnetic, optical, and other types ofstimulation intended to modulate biological activity. Stimulationdevices may be implanted in the body to modulate the activity ofdifferent tissues such as the heart, digestive system or otheranatomical targets. Alternatively, stimulation devices can be implantedwithin the brain, or within the skull, and may stimulate the brain inorder to modulate targets in the body, such as the heart, indirectlythrough the descending tracts of the nervous system. FIG. 1B shows apatient in which both a stimulator 10 c and a timer-programmer 50 havebeen implanted. The timer-programmer 50 (which may be coupled to asensor 60, such as an optical sensor) is an accessory which works inconjunction with generic stimulators in order to modify theiroperations. The stimulators 10 and timer-programmer 50 can be configuredor adapted to provide treatment by adjusting protocols according to apatient's state, automatically providing alert signals, and to otherwiseoperate according to the features of the invention as described herein.

FIG. 2A is a schematic representation of an embodiment of a stimulator10 d (e.g., similar to the electrical stimulator 10 a), which includes acontrol subsystem 20, a stimulation subsystem 22, an evaluationsubsystem 25, a power source 26, such as a rechargeable battery, and amemory storage structure such as a database 28. The control subsystem 20contains electronics which are commonly incorporated into implanteddevices such as specialized circuits for carrying out the tasks involvedin providing stimulation therapy (see, e.g, U.S. Pat. Nos. 6,066,163 and6,810,285). The stimulation subsystem 22 can include hardware needed forthe generation and transduction of different waveshapes used duringstimulation according to the stimulation protocol. For example, aprogrammable signal generator (with amplifier circuitry) capable ofgenerating charge-balanced biphasic pulse trains having programmableamplitude, frequency, and pulse width characteristics. The stimulationsubsystem can also include a signal routing circuitry for routing thestimulation signals to one or more of the appropriate contacts 15 of thestimulation conduits.

FIG. 2B is a schematic of the components of another embodiment of thestimulator 10 e and includes a control subsystem 20, a stimulationsubsystem 22, a sensing subsystem 24, an evaluation subsystem 25, apower source 26, and a database 28. The sensing subsystem 24 can provideany analog-to-digital conversion circuitry, memory, multiplexingcircuits, relay, signal processing circuitry, or other circuitry whichis not provided in the control subsystem and which is needed to obtain,process (e.g. filter), analyze, amplify, and store the sensed dataobtained from at least one sensor. The sensing subsystem 24 senses dataand performs processing and analysis according to the parameters of asensing protocol. Analysis of the sensed data can include featureextraction of time, frequency, or time-frequency domain features of thedata. The sensing subsystem 24 can calculate quantitative results whichit provides as processed data the control subsystem 24, although thecontrol subsystem can process the raw data itself 306 (FIG. 4). Theevaluation subsystem 25 is a module of the control subsystem 20 that canevaluate processed data using an evaluation algorithm that operatesaccording to a protocol, and can perform additional processing andevaluation of the data that was not accomplished in prior steps by thesensing subsystem 24.

In an embodiment of the invention, the sensing and evaluation protocolsare adjusted by a control program. For example, each protocol may beselected from a set of two or more protocols. Such selection can bedetermined by patient state which is determined when the control programthat is implemented by the control subsystem 20 operates to comparepre-set times stored in the database 28 to the time information providedby a clock 302 (FIG. 4) and determines a match (e.g., steps 70 and 72 ofFIG. 5). In other embodiments the sensing and evaluation protocols areselected based upon a patient state which is computed from sensed data(e.g., steps 116 of FIG. 8). As will be described below, time and senseddata information may both be used to calculate a patient state valuethat is then used to adjust or select a treatment protocol.

It should be noted that the conduits (e.g. 12 a, 12 b, shown in FIG. 1A)can provide both therapy delivery and sensing. For example, each contact15, can be used both as a sensor, wherein the stimulator conduitfunctionally communicates with the sensing subsystem 24, and as astimulator, wherein communication occurs with the stimulation subsystem28. The physical connection between the contact 15 and the sensing 24and stimulating 22 subsystems, can be controlled by a micro-relay orswitch which can be located in the control subsystem 20 circuitry, suchas a make-before-break double-throw relay. Alternately, as shown in FIG.1B, sensors 60 and stimulators 15 may be physically distinct, forexample, as may be the case when the sensors 60 measure optical,chemical, pressure, temperature, movement, or other physical aspect ofthe region from which the sensed data are obtained. As is illustrated,the electrical stimulation/sensing can be medicated directly by thecontrol subsystem 20, or can be accomplished by means of the stimulation22 and sensing 24 subsystems which are under control of the controlsubsystem 20, as is the case for drug delivery. If the stimulationentails the delivery of drugs, then the drug can be directly dispensedthrough the drug conduits 12 b by the stimulation subsystem 22 of thedrug delivery system 10 b.

External Timer-Programmer.

As was shown in FIG. 2B, the invention can be realized in a distributedembodiment. FIG. 3A shows an embodiment of the invention wherein atimer-programmer 50 is used to provide features of the invention. Thetimer-programmer can be (but need not be) implanted fully in the patientand can communicate with a generic stimulator 10 or its patientprogrammer. The timer-programmer 50 can communicate, via thecommunication module of its control subsystem 2 with the communicationmodule 316 of the control subsystem 20 of the stimulator 10 in order toguide treatment according to the principles of the invention. Theprogrammer 50 can contain a control subsystem 52 that is similar to thecontrol subsystem 20 of the device 10 and a database 58 containing, forexample, times at which different protocols can be selected, theparameters for each protocol, and an “alert event set”. Thetimer-programmer 50 can also include a power supply 56. Thetimer-programmer 50 does not need to have a stimulation module, as thestimulation module of at least one device 10 serves this purpose.

The timer-programmer 50 can be implanted as is shown in FIG. 1B or,alternatively, can be realized in external embodiments. For example, thetimer-programmer 50 may be incorporated into a watch-like mechanism thatserves as an external patient programmer 500 and is worn on a patient'swrist. The timer-programmer 50 can be realized in the form of a softwaremodule of an external patient programmer 400 that works with thestimulator 10. In an embodiment of the invention, the external patientprogrammer 400 and the communication module 316 of the stimulator 10each include a transceiver operable in the MISC (Medical ImplantCommunications Service) band around 400 MHz, enabling communicationbetween the devices over a range of several meters. An implantedtimer-programmer 50 can server to turn the stimulation device 10 “on” or“off”, can automatically send alerts, and can provide other features ofthe invention. The timer-programmer 50 thereby allows genericstimulators, which are already FDA approved, to provide treatmentaccording to timing or other information, even if this capability is notnormally available in the generic device 10. The timer-programmer 50contains a control subsystem 52 which can approximately contain theelements previously described for the control subsystem 20 including areal-time clock and any components not included in the device 10 whichare needed to implement the features of the invention. An externallysituated timer-programmer 50 allows for somewhat more complex controlprograms and algorithms, and as such a device would not necessarily beconstrained by the same limitations of size and power consumption as animplanted device.

FIG. 3B shows an alternative embodiment in which the timer-programmer 50includes a sensing subsystem 54 that communicates with at least onesensor 60 adapted to collect information from the patient, therebyallowing the timer-programmer 50 to adjust treatment, for example, basedupon patient state values derived from sensed data. Alternatively, ifthe implanted device has sensors, then the timer-programmer 50 can usesensed data which is obtained by the device 10 and transmitted to thetimer-programmer 50. If the timer-programmer 50 is expected to perform arelatively large amount of communication with the device 50, it mayinclude a communication subsystem 216 as a separate subsystem and,rather than using telemetry, the timer-programmer 50 can have a physicalcommunication port 218. This port 218 allows a physical connection to bemade between the timer-programmer 50 and at least one implanted device10 which is also configured with a communication port so that a physicallink can connect the two devices. A physical connection may require lesspower than using telemetry. A single-wire connection, using thepatient's body as a reference, may be used for the connection to reducecomplexity and the likelihood of mechanical failure, although it islikely that a multi-stranded cable would be implemented for providingboth efficient communication and the sharing of power.

The timer-programmer 50 can be programmed to communicated with mostcommercially available stimulators that are already designed tocommunicated with the external patient programmers provided by amanufacturer. To accomplish this, the communication subsystem 216 (asmay also be realized by 316) can include routines for identifying animplanted stimulator and external patient programmer 400, establishingcommunication, making error and parity checks, dysfunction alertroutines to alert the patient in the case of breakage, and alertroutines for automatically notifying or querying the patient abouttreatment operations that have been defined as alert events. When theprogrammer 50 has a clock, the control subsystem 20 of the stimulator 10may, or may not have a clock. FIG. 1B shows a patient in which both astimulator 10 and a timer-programmer 50 have been implanted, and whereinthe timer-programmer 50 has a sensor 60 which is used to adjust orselect the stimulation, sensing, or evaluation protocols based uponeither timing or sensed information according to the features of theinvention. When a physical connection is present, then the stimulator 10may not require its own power source, and the timer-programmer 50 cansupply power to the stimulator 10. Conversely, the timer-programmer canobtain power from the stimulator 10. In an embodiment of the invention,the control subsystem 52 of the timer-programmer 50 may function toapproximately replace a majority of the components and capabilities ofthe control subsystem 20 of the stimulator 10.

Control Subsystem.

FIG. 4 shows an overall block diagram of an exemplary control subsystem20 that allows devices to implement features of the current invention.The control subsystem implements the treatment program according to thecontrol algorithm of the treatment module 300. The treatment module 300contains the treatment program, which may be part of or interact withthe control algorithm, and implements the treatment program bycommunicating with, coordinating, and controlling the modules of thecontrol subsystem 20 and their operations. The control subsystem 20serves to realize the treatment program by controlling the stimulationsubsystem 22, sensing subsystem 24, and evaluation subsystem 25,according to stimulation, sensing, and evaluation algorithms andassociated protocols. The control subsystem 52 of the timer-programmer50 or the external patient programmer 400 can include all or some ofthese components, although these would be adapted to control a genericstimulator device 10 c rather than being located within the stimulatoritself. Accordingly, the control subsystem 20 may be implemented eitheras a single component within the implanted device 10 or exists asdistinct modules distributed throughout a system.

At various times prior to, during, or after implantation, the controlsubsystem 20 can be programmed adjust therapy in relation topredetermined times. The times may be, for example, absolute number ofcounts of the clock, relative durations (e.g., times since the laststimulation protocol was selected, time since last stimulation occurred,and cumulation amount of time stimulation that has occurred over arecent period using current protocol), or times of day. Using anexternal patient programmer 400 (FIG. 2A), the patient may adjust thetime values stored in the database 28 which are used by the treatmentprogram implemented by the control subsystem 20 in order to select oradjust treatment protocols according to specific times. For example, oneprotocol can be selected to occur just prior to when the patient usuallywakes up, and another protocol can be selected to occur after a specifictime in the evening after the patient has normally fallen asleep.Protocols can also be automatically adjusted based upon times andperiods when a patient normally eats, works, exercises, or experienceshigher levels of anxiety or depression. This adjustment can beprogrammed to occur prior to anticipated events, or during such events,and may extend until after the event ends. During the course oftreatment, the time values can be adjusted using the external patientprogrammer 400 to reflect changes in the patient's schedule, as mayoccur, for example, due to daylight saving time, travel to differenttime zones, an acute event, etc. A clock 302 of the control subsystem20, which may be a real-time clock or simply an interval timer, providestimes information which may be used in calculating a patient state valueor otherwise adjusting therapy. For example, the clock 302 permits thecontrol subsystem 20 to select a protocol from two or more protocolsstored in memory, or to adjust at least one parameter of a protocol(such as the operative stimulation protocol) based upon timeinformation.

The patient state value may be used by the control subsystem 20 todetermine that a protocol will be adjusted. The control subsystem 20 canutilize an algorithm which compares the current time of the clock totime criteria (e.g., time=11 p.m.) in order to determine the patientstate value or determine that some operation is scheduled to occur. Thistime algorithm is part of the treatment program which uses a treatmentprotocol that has parameter values, some of which are selected timesrelevant to therapy. Because the clock 302 of the implanted device candrift over time, the clock 302 used by the control subsystem 20 can beadjusted or calibrated using at timing signal that is provided by theexternal patient programmer 400.

The control subsystem 20 also contains a patient alert module 304configured to automatically provide notice to the patient of “alertevents”, using signals and obtain patient input in response to thesealert signals. The patient alert module 304 implements a patient alertalgorithm that uses patient alert rules to provide the alert signal andalso to obtain and process patient responses. The algorithm can assessif alert events have occurred, and can be informed that these haveoccurred from other modules of the control subsystem 20. Alert eventsinclude any operation (e.g., medically relevant events) which is definedas requiring that an alert signal be sent, as may be defined in the“alert event set”, which is programmed into a data base 28, or into thepatient alert algorithm itself. For example, the patient alert module304 can automatically send alert signals to notify the patient about thepending implementation of any treatment operations (which are defined asalert events) and also to await a response from the patient. In additionto the provision of therapy, when any adjustments in operation arescheduled to occur, and these are alert events, then the patient alertmodule can automatically send an alert signal to a patient announcingthe proposed adjustments. The characteristics of the alert signal whichis provided can be defined according to the patient alert algorithmusing patient alert rules of the patient alert module 304, can bedefined separately in an “alert signal set”, or can be part of the alertevent set and be stored as information that is accessed when theirrespective alert events occur.

The patient alert module 304 may cause the communication module 316 tosend an alert signal to the external patient programmer 400 which canalert the patient using its own methods and transducers. An alertsignal, such as that implemented in step 86 of FIG. 6A, can cause theexternal patient programmer to emit a visual, auditory or vibrotactilealert signal as well as text-based message. The alert signal may requirevarious responses from the patient, such as an “accept” response, a“multiple choice” response invoked by a request that the patient choosefrom multiple options, or “score” response, invoked by a request toassign a weight or score to a particular value (e.g. a response mayinclude asking a patient to rate his or her pain level on a definedscale). Additionally, the communication module 316, itself containsvarious transducers to provide alert signals in the form of auditorytones, vibrotactile signals, somatosensory electrical stimulationpatterns, and other modes and combinations, according to the alertsignal that was selected by the patient alert module 304. For example,an auditory signal which repeats 3 long beeps 2 times might signify thatthe system is going into a “sleep” mode. The alert signal can occursimultaneously with a suggested operation, at least a minute or someother defined period prior to the time the proposed operation isscheduled to occur, or can be set to occur according to patientpreference with respect to the proposed operation (i.e., the patientalert rules are configurable by the patient).

Patient alert rules include what to do if a “cancel alert” event occurs.A cancel alert rule is a type of patient alert rule that can definedboth a cancel alert event as well as operations that are invoked. Acancel alert event may cause the prior alert signal to be turned off, orreplaced, even if the patient has not provided a response. For example,a cancel alert rule may state that if the event which served as theprior alert event is no longer detected for a specified amount of time,then a cancel alert event has occurred and the prior alert signal isthen cancelled. Alternatively, the cancel alert rule can dictate thatthe previous alert signal is replaced with a different alert signal ifan alert event which has a higher priority occurs (e.g., if cardiacactivity transitions from bad to worse, causing a detection of a firstand then a second alert event, the detection of this latter alert eventcan have priority as defined in the priority rules module 312). A cancelalert event can thus result in either canceling or providing theoperation suggested by the prior alert event. A cancel alert event canbe a presence or absence of a defined sensed condition having priorityover the alert event which invoked the previous alert signal.

The patient alert module 304 operates according to patient alertalgorithm and its protocol which includes patient alert rules. Thepatient alert rules can be defined within the alert event set or beotherwise stored or accessed by the patient alert module 304. In oneembodiment, the patient alert rules consist of two types of rules, the“send alert” rules and the “patient response” rules. The send alertrules determine, for example: what information is contained in the alertsignal; what type of alert signal is sent as well as its modality; howthe alert signal is adjusted over time if a patient doesn't respond(e.g., increasing the volume over time); what alert signal occurs ifanother alert event occurs while waiting for a patient response to aprior alert signal (“overlapping rule”); whether to provide a “missed”alert signal which notifies a user that an alert event occurred withoutthe user providing a response; what to do if the patient state valuechanges or the alert event stops being detected (i.e. is “extinguished”)while waiting for the patient to provide input (“transition rule”), andwhat to do in other situation, with respect to the adjusting the alertsignal.

The patient response rules can include, for example, what to do: if apatient does not respond; while waiting for a patient to respond; if apatient accepts or rejects a proposed operation; for each response of a“multiple response” question; when a patient response is one of variouspossible values; if a patient delays an operation proposed by the alertsignal; and what to do in other situations, with respect to theadjusting the operations carried out by the device. The patient responserules also determine how long to wait for a patient's response prior toimplanting a particular operation. Patient response rules allowtreatment algorithms to operation (e.g., provide therapy) even when apatient doesn't respond, such as may occur when the patient is in theshower, in a loud restaurant, or if the programmer is out of range.According, “no response” must be included a possible type of patientresponse. In the case of insulin delivery, if the patient doesn'tprovide an “accept” response to an alert signal which requests userapproval for a dose which is above (or below) a specified level, thesystem must know what to do and can not simply halt its operation (e.g.,the evaluation of incoming data and provision drug delivery) whilewaiting for a user response. In the case of a diabetic or cardiacdisorder, abstaining from a proposed therapy indefinitely, while waitingfor a user response, can cause a serious medical condition to arise. Onetype of patient response rule may state that a “no response” causes theintensity level of an alert signal to be increased over time accordingto a function which may vary with an alert signal type. Another patientresponse rule may state the “no response” causes the device to wait fora specified amount of time and then accept, reject, or modify, theproposed operation. Another “no response” patient response rule may waitfor a patient response unless a type of additional alert event isdetected within a specified amount of time (i.e., a “cumulative” rule).The cumulative patient alert rule may also dictate that the actionsuggested in the prior alert signal occurs, even without the userresponse. The user or physician can define the various patient alertrules and combinations of rules which will be utilized during treatment.

The patient alert rules can be designed to accommodate a large number ofpatient input responses. Some types of patient response are: “accept”,in which the proposed operation occurs; “accept duration”, in which theproposed operation and subsequent operations of the same type areaccepted for a specified duration; “adjust”, in which the user modifiesthe proposed operation; “delay”, in which the user accepts the operationbut delays its onset by a specified amount; “remind” in which the alertsignal is repeated at a later time; “reject” in which the operation isrejected, “reject duration” in which the operation contained in thealert signal is rejected and all similar alert events are automaticallyrejected for a specified duration; and “more info” in which the userrequests more information be provided before providing a patientresponse. The duration of a response condition can be increased if apatient provides a “delay” or “remind” input.

The patient alert module can store a limited history of past alerts inthe database 28. The treatment program can cause the patient alertmodule to adjust alert signals, or cause an operation to occur withoutpatient input based upon alert history, and according to patient alertrules. For example, if a selected number of alerts are sent within aselected amount of time (i.e., a “cumulative” rule), if the alert eventsbecome larger or more numerous over time (“trend” rule), or if asubsequent alert is issued while waiting for a prior alert (i.e., a“overlapping” rules, which can be implemented as a type of a cancelalert rule) then an operation, such as delivery of a proposed treatment,which may normally be an alert event may occur without patient input, oraccording to a response rule which waits only a slight period forpatient response. In one embodiment, response conditions can be labeledas either positive or negative. A positive response condition may beevaluated as true due to a positive explicit response from the patient(“patient input=accept”), an expiration of a rejection time limit, apresence or absence of a defined sensed condition having priority, orany of numerous other possibilities. A negative response condition maybe evaluated as true due to a patient's explicit request to reject achange, an expiration of an approval time limit, a presence or absenceof a sensed condition having priority, or any of numerous otherpossibilities.

Various other forms of notification, according to varying degrees ofurgency, are possible in a system according to the invention. Forexample, if the patient is likely to be disturbed during sleep by anaudio signal, and such a high level of intrusion is unnecessary, thesystem may send a text alert signal to the programmer 400, allowing thepatient to check for alerts when the patient awakens. In such a case, aflashing light may also be provided on the programmer 400, similar tovoicemail indicators found on telephones.

The control subsystem also contains a processing module 306, while canbe configured to extract features from the sensed data, as well ascalculate statistical properties of these features such as mean,standard deviation and z-scores. The processing module 306 can alsoprovide the database 28 with the calculated values in order to provideself-norm reference data which may be used for such purposes ascalculation of the current patient state and determining if a patientstate has changed, or storing the number of detected events (e.g., alertevents) which have occurred over a recent period. The processing module306 can also include filtering, classification, template matching, andother signal analysis modules. The processing module can process senseddata to provide processed data which can be used by the control lawmodule 308 to generate output stimulation signals according to thecontrol law selected in the stimulation protocol that is implemented bythe control subsystem 20. The algorithms of the processing module can beutilized by the evaluation module 25 in the evaluation of sensed andprocessed data.

The control subsystem 20 also contains a treatment criteria module 310,which assists the evaluation subsystem 25 in comparing, for example,processed data or time information to treatment criteria. The treatmentcriteria module 306 loads treatment criteria values from the database 28according to the selected evaluation protocol. The treatment criteriamodule 306 can detect medically relevant events which result inresponsive stimulation. The treatment criteria module can includetreatment benefit criteria which assist in calculating measures that arereflective of, for example, whether treatment is decreasing or otherwisealtering the number or severity of detected medical events, compared to(mean values of) a reference treatment period.

The control subsystem 20 also contains a priority rules module 312,which can implement priority rules which may be set according to apatient's preference. A priority rule can be adjusted by automaticallysending an alert signal requesting the patient to assign priority to oneof two operations. Further, the priority rules module 312 can setpriority rules dynamically according to patient state or for differentoperations. For example, for a “stimulation off” operation timeinformation can have priority over sensed data, while for a “stimulationon” operation the opposite can be true.

The control subsystem 20 also contains a patient state module 314, whichdetermines the patient state using data from the device (such as timedata, patient response data, and sensor data) processed through thepatient state algorithm and according to the patient state rules whichmay also incorporate the priority rules of the priority rules module312.

The patient state rules govern how to define and classify patient stateand can also include rules about what operations may occur according todifferent states.

The control subsystem 20 also contains a communication module 316, whichcontains telemetry algorithm and hardware for communicating betweendifferent components of the therapy system such as the patientprogrammer 400. The module 316 also can provide dysfunction alerts incase the system encounters an internal error, is low on reserve power,or when it can contact the patient programmer 400. For example, thedevice may begin to emit an auditory signal which is audible by thepatient when an alert signal has been triggered but the device 10 findsthat it can not successfully communicate by telemetry with theprogrammer 400. The communication module 316 can then implement theinstructions of the patient alert module 304 in order to send andreceive information from the patient.

The control subsystem is operated according to a treatment program 300that implements a treatment algorithm. The treatment program 300controls the operations of the components of the system to providetherapy. The treatment program coordinates the various modules of thesystem to work together so as to provide treatment. For example, thetreatment program can rely upon the priority rules module 312 to causethe patient alert module 304 to automatically issue an alert signals,for only one of two approximately simultaneous alert events, accordingto patient alert rules, and may detect this event based upon anevaluation algorithm of the evaluation subsystem 25 that is selected bythe patient state module's 314 algorithm operating in accordance withpatient state rules. An example of how the treatment program combinesfeatures of the invention to provide improved therapy is shown in FIG.11 a.

The different protocols and their parameter values as well as otherreference information utilized by the device 10 are stored and retrievedfrom the control subsystem's memory which can be implemented, at leastpartially, in the form of a database 28. The database 28 permits thecontrol subsystem 20 to obtain information such as stimulationparameters for various stimulation protocols, self-norm data, and otherinformation relevant to providing therapy. Such parameters and data maybe pre-defined across a patient population, tailored by a physician orexpert system for a particular patient's needs, or constantly refined bya system according to the invention; combinations are also possibledepending on clinical need.

The control subsystem can also include various components such asprogrammable memory, a microprocessor, additional timers/clocks,multiplexors, switches/relays and other components which are found inthe control subsystems of most implantable neural or cardiac stimulatorsas is known well to those skilled in the art. Although shown as separatecomponents for purposes of illustration, the components of this andother figures provided within this specification can generally berealized on a single circuit board, and even a microchip which containsspecialized circuitry for amplification, digital-to-analog conversion,digital and analog signal processing, memory, timing, clock, andcommunication circuitry which are powered by a power source. When thestimulator provides drug therapy, the electronics can supply control of,and power to, a pump for dispensing one or more drugs stored in areservoir assembly according to the stimulation protocol. Havingdescribed the components of the systems the associated methods will bedescribed which allow the implementation of the features of theinvention during its operation.

Priority Rules

The control subsystem 20 may automatically select a protocol accordingto patient state in a closed-loop manner. For example, the sleepingprotocol may be selected if evaluation of time data indicates that thepatient is sleeping. Sensed data may also be used as an alternative to,or in conjunction with, the time information provided by the clock ofthe control subsystem 20. Accordingly, stimulation system can use eithertime or sensed data to determine patient state and provide closed-loopadjustment of stimulation treatment. When time information and senseddata information are in conflict as to what the current patient statevalue, priority rules can be used to resolve this conflict.

In the '784 application, referenced above, when time information isavailable, the stimulator 10 generally operates according to the sleepprotocol at night and the awake protocol during the day, as indicatedwhen the clock time information matches predefined times which defineawake and sleep periods. Similarly, in the current invention when senseddata are also available, unless there is a clear indication that thepatient is in a state other than that indicated by the time information,the patient state rules of the patient state module 314 can indicatethat the time information has priority over sensed data in thedetermination of patient state by the patient state module 314.

While a default protocol of the patient state module sets a patientstate rule that is a priority rule in which time has priority oversensed data, the patient state algorithm of the patient state module 314can select a different priority rule if a patient state criteria for thesensed data is met which is stringent enough that the patient is almostcertainly in that state. FIG. 5, shows an embodiment which is compatiblewith this method. First the clock is checked 70 and patient state isderived as is indicated by the time information 72 stored the database28. Next, data are sensed 74 and the evaluation of sensed data indicatesa present state 76 based upon sensed data. Next the patient state basedupon time information is compared to the patient state as derived bysensed data 78. If the patient state based upon time information iscompatible with the protocol selected based upon sensed data information80 a then the patient state is used to select or adjust the protocolwhich is used to provide treatment 84. Alternatively, if the patientstate which is indicated by time information is incompatible with thepatient state indicated by sensed data information 80 b then theprotocol which is used to provide treatment 84 is selected based uponpatient state rules implemented the patient state algorithm 82.

A patient state such as “asleep” can be determined based upon measuresof sensed data related to eye movement (e.g., to detect REM sleep),blink rate, and position (e.g. to determine if the eyelids are open orclosed), and respiration or cardiac or motion activity. There are alsoelectrographic markers of sleep observable in the brain. For example, adetermination of patient state can occur wherein if the patient's eyesare shut for longer than a specified period, as can be defined in apatient state criterion, then sensed data can have a priority and thesleeping protocol can be selected. The system may utilize an evaluationprotocol that evaluates patient state using compound patient statecriteria in two or more operations. For example, both an “eye shut”criterion, and an EEF criterion where a relative power shift to thelower frequency range is over a specified amount, are met (or are faileddepending upon the logic of the comparison operation) in order to setthe priority rule to give priority to sensed data in order to set thepatient state value to “sleeping” and invoke the sleep protocol.

The patient state algorithm which is implemented by the controlsubsystem 20 of the current invention can dictate patient state and isdetermined by time information rather than sensed data informationunless the state information meets patient state criteria that mostcertainly indicated the patient is in a particular state (e.g. awake orasleep). Some of the references cites above describe a feature where athreshold parameter used to determine patient state from sensed data maybe adjusted by the physician or the patient to provide increasedbenefit. Further, the patient has the option of manually turning thestimulation system “on” or “off”.

The current invention improves upon known methods by providing atreatment program that automatically and dynamically selects differentpriority rules for different operation and for different points of theday, such as can be implemented as patient state rules by the patientstate algorithm. For example, although a patient may be asleep whennapping during the day and when sleeping at night, the patient may onlywant the sleeping protocol to occur during the night, even if senseddata certainly indicate that sleeping is occurring. Except on the basisof time, it is almost impossible to design the threshold criteria usedby the patient state algorithm to distinguish between regular sleepingand napping. Further, the two activities may be identical with respectto many measures. By temporally adjusting priority rules during specificperiods of the day the patient does not have to repeatedly adjust thethresholds used to detect different patient states during the course oftreatment. This is also an advantage over known approaches because itdecreases the computational requirements of the implanted device whichmight be needed to distinguish similar states of the patient andimproves therapeutic benefit to the patient. Additionally, during timeswhen time information has been defined as having priority over sensorinformation, the sensor information can be turned off, which can savepower usage. Similar to priority rules, patient state or treatmentcriteria can be adjusted at different times.

The methods of the invention also include automatically sending an alertsignal to the patient when time data and sensed data informationcontradict each other, wherein the patient's response to the alertsignal determines which priority rules is selected. The priority rulescan also be applied to resolve conflicts between chemical and electricaldata. The selection of a priority rule can be contingent upon athreshold criterion related to patient state wherein only if thethreshold is exceeded does the priority rule get implemented. Forexample, normally sensed data information related to electrical activityis preferred to sensed data information related to chemical levels,unless these levels are above or below a level defined in the criteriainvoked during a particular patient state. In addition to patientactivity defining patient state, electrical or chemical activity servethis purpose. For example, a patient state can be classified as a “low5-Ht” patient state, when serotonin levels sensed at one or more sensorsdrop below a specified criterion.

Priority rules can be used to resolve conflicts encountered in providingor adjusting treatment, especially with respect to adjusting thestimulation which is provided. The sensed data from two or more sensorscan e evaluated using logical operators in a conditional manner. Forexample, if data sensed at a first sensor and a second sensor are bothabove specified thresholds, then stimulate in a particular manner. Thiscan be considered an example of using a “complex treatment criterion”according to the invention. While in the '328 patent multiple types ofsensed data including electrical and chemical activity are used toresponsively provide stimulation, no mention is made of want to do whendifferent types of data indicate contradictory information, such asincreased and decreased treatment benefit. This can be addressed usingpriority rules. Similar to determination of patient state, theevaluation protocol can be governed by priority rules of the priorityrules module 312 when determining if responsive stimulation oradjustment of the treatment is provided. The use of dynamicallyadjusting priority rules should enable therapy to incorporate, and adapttreatment on the basis of conflicting information. In an embodiment ofthe invention, a device can use its patient alert module toautomatically request that patients select a priority rule or make otherdecision which resolves conflicting information. It will be noted thatvarious criteria may be evaluated within priority rules according to theinvention, including but not limited to treatment criteria, timecriteria, and patient state criteria.

Semi-Automatic Treatment with Automatic Patient Alerts

Modern implantable stimulation devices are increasingly incorporatingtreatment programs that provide more comprehensive types of automationin controlling stimulation. Both the providing and adjusting treatmentmay occur in a fully automatic fashion. For example, responsivestimulation is stimulation which is triggered in response to sensed datawhen analysis of the data results in detection of one or more abnormalmedical events. Adjustment of the stimulation that is provided can bebased upon characteristics of a detected event such as the magnitude ofobserved activity in a device operative to respond to epilepticseizures, or can be based upon some related state of the patient.Although treatment algorithms may utilize time information, or evaluatesensed data, to accurately determine the state of the patient and thenautomatically change the treatment protocol, this may not universallywork well for all patients. Further, as mentioned, conflictinginformation can pose a problem: sensed data may sometimes indicate aparticular state (a person is sleeping) while time data indicates that adifferent state is occurring (a person is awake). It is difficult for animplanted device to accurately and automatically resolve conflictinginformation, and adapt to variations in the patient's daily routine, orotherwise anticipate the therapy preferences of the patient. Rather thancreating increasingly complex routines for automatic, closed-loopcontrol, semi-automatic methods may provide improved therapy by allowingpatients to guide therapy by responding to automatically generated alertmessages.

A central factor in providing therapeutic stimulation is the variabilityof the patient's daily routine. Currently, there is no knownsemi-automated manner for easily enabling a patient to modify treatment,in instances when the patient intends to deviate from an expectedschedule, for which the pre-designed program was configured. Forinstance, a patient may choose to remain awake for several hours pastthe normal time when he/she falls asleep but may forget to change thesetting for the implanted device. If a neurostimulator automaticallypowers down at 9 p.m., while the patient will not go to bed until 11p.m., the clinical benefit of the implanted device is decreased. Asecond issue is that more complex algorithms require more power andresources and are complex to adjust for individual patients. Further,patients may have different preferences at different times and it isimpossible for the algorithm to anticipate these preferences.

While time and sensed data information can sometimes be resolved by analgorithm using priority rules, a device may have trouble automaticallydisambiguating two patient states which are physiologically similar,such as being in REM sleep or being awake, being nervous and beingexcited. Although these are distinct states, these are alsophysiologically similar in certain respects. While the implanted devicemay automatically evaluate the patient's state or symptom severity thesubsequent automatic operations may not always be desired. For these,and other reasons, fully automatic methods for adjustment or provisionof treatment can be less desirable than semi-automatic methods whichrequest a patient's approval prior to performing certain operations. Byautomatically alerting the patient to a proposed change in thetreatment, the implantable device of the current invention offersadvantages over both fully automatic, and patient initiated,non-interactive, methods.

An automatic alerting method provides significant advantage since it canprovide treatment which anticipates a future need, symptom of thedisorder, or patient state. Although a patient may not need therapy at aparticular time as may be indicated by evaluation of sensed data,initiating stimulation prior to the need arising can act to attenuate orprevent manifestation of an unwanted symptom. For example, initiatinggastrological treatment at a time that is an hour before when thepatient normally eats can deter an unwanted event that may normallyoccur during eating, however, there is no need to do this if on thatparticular day the patient does not intend to eat, or to eat at a usualtime. In this case, relying upon sensed data to adjust stimulation willlikely not provide stimulation to treat the event until itsmanifestation, while stimulation which is suggested according to a timeof day or time since last eating may improve therapeutic benefit. Thecurrent invention therefore uses automatic alerting to providepre-emptive stimulation methods that are an advantage over knownapproaches. Pre-emptive alert messages include sending an alert signalwhich includes asking a patient to respond to anticipatory questions,such as, “will you eat in the next half hour?”, “do you feed a slightaura?”, “do you have a slight headache?”, “has your feeling of anxietyincreased slightly?”. Accordingly to the patient alert algorithm, whenthese questions are answered in the affirmative (e.g., patientinput=accept) the device can provide anticipatory stimulation, such as astimulation program which slowly begin to stimulate a target thatmodulations the digestive system in a manner which will assist thesubsequent digestion process. Instead of developing complex algorithmsto accurately detect slight changes related to the disorder (e.g. aslight increase in anxiety) or symptom onset, the device can use methodswhich correctly detect these at least, for example, 50% of the time, andcan be made accurate by simply automatically sending an alert signal tothe patient to confirm or deny a treatment operation that is based uponthese changes.

A stimulation system which automatically sends alerts throughout theday, or in the middle of the night, to the patient may provide moreaccurate therapy but may be unpleasant to the patient. The automaticalerting methods do not necessarily occur for all treatment operations,but can rely upon an alert protocol in which alerts are only send duringcertain times and only for certain types of operations that arespecified by the patient. These operations can be, for example,adjusting a stimulation parameter in a manner which may produce unwantedside-effects, such as increasing voltage above a specified amount;adjusting the patient state value; resolving two types of contradictoryinformation; and responsively providing stimulation according toselected medical events. In addition to changes in patient state,detection of a medical event can cause the control subsystem 20 to sendan alert message 86 before providing responsive stimulation.

The semi-automatic methods of guiding the treatment using automaticalerting include a number of alternative embodiments. The method caninclude: alerting the patient to changes; querying the patient aboutproposed changes that are to be made; sending alerts to obtain patientinput information to resolve potentially contradictory information; andalerting in response to a number of other scenarios. In response to theautomatically generated alert issued by the system, a patient canprovide any number of patient responses and the device 10 must be ableto address these different possibilities. These semi-automatic protocoladjustment methods are shown in the embodiment of FIGS. 6A and 6B, whichcan be used instead of, or in addition to the fully automatic methods,such as that shown in FIG. 5. It is understood that the patient, doctor,or treatment program can toggle the system to work in a fully automaticmode, a semi-automatic mode, or a manual mode where the patientdetermines the characteristics of the treatment protocol implemented bythe treatment program.

FIG. 6A, illustrates a method of providing semi-automated therapy to apatient which is guided by patient input provided in response toautomatically sent alert signals. In this example, the control subsystem20 of the device 10 determines that an alert event has occurred forwhich an alert signal should be sent 85 (e.g. this can occur accordingto the patient alert rules of the patient alert module 304). In step 86,the patient alert module 304 of the control subsystem 20 automaticallyissues an alert signal using the communication module 316. A number ofconditions (determined by patient alert rules) may cause the patientalert module 304 to issue an alert signal in step 86. For example, ifthe patient state value becomes different than a current patient statevalue and indicates a change in the therapy program is needed. Thepatient state algorithm may use the patient state rules to instruct thatthis action occur based upon the change in patient state. Alternatively,step 85 may occur if the patient state algorithm is unable to determinethe patient state and has issued a request for information from thepatient such as defining the current patient state, or choosing betweentwo or more patient states, or simply providing information which willallow the patient state algorithm to define the patient state (e.g.selecting a priority rule). An alert can also be sent prior to adjustingthe stimulation (e.g., increasing voltage by 1 volt) or responsivelyproviding stimulation. The alert can be accompanied by a suggested aoperation which is scheduled to be executed. For example, the system 10can send the following alert message to the external stimulator,“protocol=sleep, delay=1.5 hours, duration=6 hours?” which means that itwill select the sleep protocol in 1.5 hours from present time, and willmaintain that protocol for 6 hours. The alert signal can also include asummary of why this decision is being made (e.g. “Time=10 p.m.”).

As shown in FIG. 6A, in response to the alert message there are a numberof outcomes 88. The patient alert module 304 or control subsystem 20must be able to function for according to all of these possibleoutcomes. The patient can either confirm this change (e.g. by pressing a“yes” key on the external programmer or using a magnet to actuate asensor on an implanted device according to a “yes” pattern which isdifferent than a “no” pattern) 88 a, or can confirm a change aftermodifying a value of the change 88 b. For example, the patient canincrease the duration of the sleep protocol to 8 hours in the case whereit is a Saturday night and the patient wishes to sleep late Sundaymorning. Further, the patient can delay this change by an additionalamount 88 b. Alternatively, the proposed change can be rejected by theimplantee 88 c. If the implantee accepts the change 88 a, or adjusts thechange 88 b, then the treatment program is adjusted accordingly 90 a, 90b. If the patient rejects the change 88 c, then the treatment isnormally not altered 90 c, although what occurs exactly in 90 c dependsupon the “patient reject” patient response rules implemented by thetreatment program. In the case where the patient neither confirms norrejects the alert message 88 d, then the change suggested in the alertmessage can either by automatically accepted or rejected based upon thepatient alert rules for the alert event, as can be defined in a defaultmode that can reflect the patient's preference. If a patient does notrespond, the “no response” rules may operate in a manner that assumesthat an alert message was missed (e.g. a send alert rule can dictatethat a blinking light may be activated on the external patientprogrammer). The reliance upon automatically generated alert messages isadvantageous since it is a semi-automatic compromise between purelymanual adjustment methods and fully automatic adjustment methods, thelatter of which may not occur in line with patient needs or wishes.

The method of FIG. 6A illustrates an exemplary method in which animplantable stimulation system 10 semi-automatically adjusts a treatmentwith the assistance of patient input. The first step is to automaticallydetermine that an alert should occur. The next step is to alert thepatient 86. The next step is to wait for a response from the patient.This is referred to as waiting for a “response condition” to beevaluated as true, where the program waits a selected amount of time forthe patient to provide a response 88 (which may be set to zero secondsif no delay is to occur). There are two alternatives that can occur inresponse to an alert signal. If the patient responds 88 a, 88 b, 88 cthen the therapy occurs according to the patient input 90 a-99 c. If thepatient doesn't respond 88 d then after a selected time interval aproposed operation will either occur or not occur, according to thepatient response rules of the treatment program 92. As shown in FIG. 6B,the response condition is set to false until the patient inputs aresponse 89 a or until a time period expires if the patient doesn't makea response 89 b or if sensed data reach some specified criteria. In thisexample the patient response rule for event alert signal indicates thateither patient input, expiration of time, or sensed data exceeding a“cancel alert” criterion will cause the response condition to beevaluated as true and cause steps 89 a or 89 b to occur. When a patientfails to make a response then the treatment can occur according to “noresponse” rules 92. If the “no response” rule implements a preferencefor an event to occur if the patient doesn't respond within a givenwindow then the proposed adjustment may occur in step 92. If theresponse condition remains false because the time of expiration has beenset to a very large value, then the system can simultaneously continueits operation according to patient response rule preferences set by thepatient or physician with respect to different alert messages. Further,the response condition can be set to true if during the waiting period,the device determines that there has been another change in patientstate (using a “transition” patient alert rule), or other change hasoccurred, which causes the original alert signal to no longer be valid.

The control subsystem 20 according to the invention sends alert signals,or refrains from sending alert signals, in particular manners accordingto the send alert rules of the patient alert module 304. The alertmodule may operate according to an alert protocol that ensures that thealert signal is either repeated or not repeated, in a particular mannerwhile waiting for a patient to respond. For example, if an alert signalwas recently sent, then the subsystem can use a send alert rule thatprevents another alert signal from being sent to a patient until after aspecified delay. This will deter the system 10 from sending repeatedalerts, as might occur if the patient rejects a proposed adjustment inthe treatment protocol, and the alert event that triggered the alertpersists for some time. The patient can not only delay the actuation ofa proposed adjustment in treatment for some selected period, the patientcan also determine a period during which a treatment protocol can slowlytransition from one protocol to another so as not to cause an adjustmentthat too rapidly for the patient.

The following events, among numerous others, can be defined as alertevents which act to trigger alert signals 85: the measurement andevaluation of sensed data; detection of an unwanted medical event;failure of sensed data to meed a criterion; a predefined time-pointmatching the current clock time information; a relative time-periodhaving elapsed; and, a change in patient state. Some events that canusefully be defined as “alert events” are events that potentially would:result in adjustments to the treatment protocol; result in delivery ofstimulation; or perform an operation which would be assisted by inputfrom the patient. Some examples of times that might cause a change inpatient state and/or stimulation to be adjusted are: time since an event(e.g., last eating); cumulative time awake; cumulative time asleep;cumulative time since last voiding of bowel/bladder; cumulative timesince last insulin delivery; time when eating normally occurs; time whensleeping normally occurs; time when anxiety normally increases; timewhen depression normally increases; and, times related to a patient'smenstrual cycle.

The adjustments proposed by the alert signal could be anything in thetreatment program, however, some illustrative examples are: a proposedadjustment in the treatment protocol which includes turning off orattenuating activity of the stimulation and sensing subsystems; anadjustment to the evaluation protocol (e.g., changing a treatmentcriterion) a proposed adjustment to the treatment protocol including themagnitude of the adjustment, the duration of the adjustment, the rate oftransition to the adjustment, and at least one location at which theadjustment will occur.

An alert signal can be triggered if an alert event is defined as a“treatment benefit” criterion failing to be satisfied, since thisindicates that the treatment is not providing benefit successfully inrelation to the criterion (e.g. the number of detected medical events isincreasing over time). Treatment benefit criteria can be evaluated toproduce values indicative of successful or unsuccessful treatment. Otheralert events can be defined where unsuccessful treatment occurs if anumber of specified medical events are detected within a specifiedamount of time, or if the number of events per unit of time increasesmore than a specified amount. An alert signal which is automaticallygenerated due to a treatment benefit criteria value indicatingunsuccessful treatment may contain a an indication of what criterion wasfailed and can also include a proposed adjustment according to thetherapy algorithm of the control subsystem 20. For example, if tremorsize has increased above a certain level for a specified duration, thenan increase in the stimulation voltage compared to what has beenpreviously used may be suggested.

Patient State.

In FIG. 5, the present state of the patient is determined in step 76using sensed data which is obtained in step 74. It should be noted thatstep 76 can include a number of methods of evaluating sensed data as iswell known such as using a discriminant or other classificationequations, pattern matching algorithms, or threshold criteria which canbe statistical criteria such as guard-bands and confidence limits. Thedetermination of patient state can also be accomplished by comparing thecurrently sensed data of a patient to past patient sensed data (e.g.,using a self norm). In this manner, present state is not necessarilydefined as a particular state, in and of itself, but is rather definedas simply different from a previous state, and can be defined inrelation to that state. The change between the current state and theprevious state can determine the type of treatment adjustment whichoccurs, as is dictated by the rules implemented by the patient statealgorithm of the patient state module 314. However, regardless of themethod used to define patient state or detect changes in patient state,the method can include a step in which the change is defined as an alertevent and the device automatically issues an alert message to thepatient to attempt to gain the patient's assistance in directingtreatment by providing patient input in response to the alert.

FIG. 7 and FIG. 8 show two alternative embodiments which generallydemonstrate that a patient state can be calculated using sensed datainformation which is then used to adjust treatment. The method of FIG. 7utilizes a change in patient state, rather than the patient state valueitself, in order to determine how treatment will be adjusted. Ratherthan a patient state being defined as “running”, “sitting” etc, themethod only utilizes a difference between a current state and areference state, according to one or more patient state criteria of thepatient state module 314. If a change has occurred, the program mayadjust treatment according to rules of the patient state algorithm. Asis shown in FIG. 7, the sensed data are collected 100 for a specifiedduration, such as a 5-minute window, and are processed to providereference state data 102. A reference state may be statistically definedby processing the sensed data using the processing module 306 to obtaina mean and standard deviation or may be otherwise defined in astatistical or non-statistical manner. New sets of sensed data are thensubsequently collected 104, and are processed to define a present state106. The present state is then compared to the reference state 108, andthe comparison determines the present state to be either the same 110 ordifferent 112 than the reference state. For example, if a measurement ofthe present state data 106 data is more than 2 standard deviations fromthat measurement in reference state data 102 then a change of state canstatistically defined as having occurred at about the p<0.05 level. If achange of state has occurred according to the criteria defined in thepatient state algorithm of the control subsystem 20, then a newtreatment protocol can be selected in a pre-determined manner accordingto patient state rules. For example, a parameter value of thestimulation protocol can be increased proportionately based upon acharacteristic of the present state increasing relative to the referencestate. The treatment program may cause the reference state to be updatedin step 115 according to the treatment protocol. For example, after anumber of iterations of the process have occurred, after a certainamount of time has elapsed, or based upon a criterion such as thepresent state of the last process being different than the referencestate. When the step 115 results in a “true” result then reference dataare again sensed 100, while a “false” result causes this step to beskipped and the routine reverts to step 104. Automatically sending analert message may occur between, for example, step 112 and 114, byperforming approximately the method of FIG. 6A.

Alternatively, rather then using change criteria, patient state can bederived from the sensed data by classification of this data. In FIG. 8classification of a patient's state can automatically guide theselection of protocols. In one embodiment, the process can start at step104 where data are sensed to derive the present state. After the dataare processed 106, the present state is compared to a database ofreference states which were previously defined (e g. in steps 100, 102)or which is defined occasionally when step 115 is set to true, and theprotocols (e.g. stimulation, evaluation, and/or sensing protocols) arechosen based upon a classification of the present state 113. Forexample, the present state can be classified as one of the referencestates that the present state most closely approximates, where each ofthe reference states is associated with a specified protocol. Theclassification of the present state into one of two or more referencestates can occur using a number of classification strategies as isknown. For example, sensed data may be submitted to a template matchingor discriminant algorithm in which class membership (classification ofthe present state as one of the reference states) is determined by thegroup to which the highest probability score is assigned. The protocolassociate with the classification is then selected 116, and used toprovide treatment 118. It is clear that the methods of FIG. 7 and FIG. 8can he used in a system which also defines patient state based upon timeinformation by inserting these methods, with slight modification, intothe method of FIG. 5. For example rather than step 118 of FIG. 8.occurring step 78 of FIG. 5 can be invoked. These and other methods oftreatment can be used to adjust the stimulation protocol and can also beused with the methods described in the next section which adjust thesensing and evaluation protocols.

Lastly, it should be noted that methods that use patient state valuescan be applied to systems which use a plurality of stimulation devices.For example, rather than simply turning a stimulator on or off, whenmore than one stimulator is used, the methods performed may leveragethis configuration to provide improved therapy. In one method duringstimulation which occurs with more than one stimulator (e.g., bilateralstimulation) the stimulation can be turned off in an alternating mannerwith respect to the multiple devices. For example, a brain stimulationprotocol for each hemisphere of a patient's brain can cycle inapproximately a 24 hour period rather than the 12 hour period usuallyused so that stimulation is turned off to each hemisphere every othernight. Alternatively, the two stimulators can switch from “on” to “off”,every hour, in an alternating manner so that one of the stimulators isalways on. In order to ensure that the clock times of the twostimulators are synchronized, and compensate for any error insynchronization, this type of cycling by a network of neurostimulatorscan be coordinated by an external patient programmer. These methodsdecreases energy usage and also address issues such as adaptation whenproviding neurostimulation. Further, the methods incorporating patientstate can be applied uniquely within each stimulator, or data pooledfrom all stimulators can be utilized by the method in the determinationof patient state.

Adjusting Sensing and Evaluation Protocols.

It will be noted that a number of advantages can be obtained by shuttingoff or adjusting the evaluation and sensing protocols as well as, orinstead of stimulation protocols. However, known systems and methodsonly halt the application of therapy and tend to ignore the operationsrelated to sensing and evaluation of data. Generally, evaluationprotocols are not modified in order to change the types of events thatare detected. For example, in known approaches, thresholds used by anevaluation program to detect an electrophysiological signature of tremoror pain are not changed due to patient state (e.g., increased duringsleep).

In one embodiment, a system according to the current invention is becapable of adjusting the sensing and evaluation protocols (e.g.locations, rate of occurrence, or duration) rather than only adjustingthe stimulation protocol. In FIG. 5, rather than simply halting orotherwise adjusting the stimulation of the device, patient state can beused to adjust the sensing and evaluation protocols in step 82. Byaltering the evaluation protocols at different times, different types ofdetected medical events can lead to stimulation treatment, and therebyprovide improved and appropriate therapy. Two or more protocols that maybe selected based upon time of day, may utilize different treatmentcriteria to provide treatment for different symptom characteristicsduring different patient states.

In the current invention, the evaluation protocol, which is used toevaluate the sensed data, may be adjusted based upon patient state(e.g., steps 114 and 116 of FIG. 8). Tremor magnitude, such as powerwithin a frequency range that corresponds to the primary oscillations ofthe tremor, and the treatment criterion used by the evaluation protocolof the treatment program can dictate that if the tremor magnitude isgreater than a first specified threshold that stimulation should occur.If the patient state indicates that the patient may be sleeping then thetreatment criterion may be adjusted so that a second threshold is used,which is larger than the first threshold. Patient state can be used tocause responsive stimulation to occur in response to events which exceeda second threshold (e.g., only larger tremors, which could awake thepatient will result in responsive stimulation the patient is sleeping).When a sleeping evaluation protocol is used, the treatment criterionused to detect a sufficiently large tremor may be set by automaticallysending an alert, prior to the patient falling asleep, which requeststhat the patient specify the 2^(nd) higher threshold which is to beused. If the patient experienced increased symptoms during thatparticular day, the patient may decide to set the 2^(nd) higherthreshold lower, or higher, than what is normally used, according to theprevious experiences of the patient.

The type of sensing, duration of sensing, rate of sensing, or otherparameter which guides the sensing protocol can be adjusted based uponpatient state. For example, when the patient is sleeping the sensingduration can be decreased by a clinically or operationally significantamount, e.g. by 30% or more of what is normally used when the patient isawake. Additionally, because the sensed data must be processed andevaluated, decreasing the sensing operations will also result in lessenergy being used to process the sensed data and extract the relevantfeatures that are used to provide treatment.

During therapy, there are periods when data should not be sensed, or atleast sensed data should not be evaluated, such as during physicalactivity when large muscle activity can interfere with the accuratesensing of the data. If earlier processing of the sensed data indicatesa patient state in which data should not be evaluated, then more complexevaluation routines may be halted. This is different than allowing theinstrument to process the data, and then simply ignoring the results inthe case where, for example, EMG activity is overwhelmingly confoundedby extrinsic or otherwise irrelevant factors (such as artifact andnoise), thereby preventing the processed data from being sensiblyevaluated. Further, in some instances, sensed data should not becollected during certain times. For example, sensed data can be used tocompare the efficacy of two protocols, as could occur in order to selectthe protocol that provides improved suppression of symptoms. In thisinstance, the sensed data should be collected and evaluated only whenthe patient is in a similar state (e.g. awake and relaxed in bothstates). In one embodiment, the performance of at least 2 stimulationprotocols is evaluated, wherein the sensing and evaluation during asecond state only occurs when the patient is in a similar state to afirst state, and the first state occurring during a period when apatient state meets specified criteria which are defined to provide anaccurate estimate of therapeutic efficacy. In order to decreasevariability of sensed data that is unrelated to the efficacy of atreatment, sensing and evaluation can occur only when patient stateinformation indicates that a patient is in a desired state, e.g.,relaxed, sleeping, or even in a particular sleep stage. Accordingly, inFIG. 8 steps 15, 100, or 104 may be delayed, or adjusted, based uponsensed data or a patient state value, in accordance with this principle.

One way to reduce the number of stimulation permutations which arepotentially used, and to improve therapeutic benefit is to have adefault program which is conditionally changed as in the '286 patentapplication. Another method is to associate different sets ofstimulation protocols with different sets of sensing protocols so thatstimulation protocols which are possibly available are determined basedupon the sensing or evaluation protocols that are chosen. The pairing ofsensing, evaluation, and stimulation protocols using “S-EV-S set” rulesis a feature of the present invention. For example, if the evaluationprotocol used in the sleeping protocol is designed to only detect largetremors, which surpass a second higher threshold, then stimulating witha protocol designed for smaller tremors will cause an unnecessary delayin treatment. For example, using a protocol which is normally used whenthe patient is awake, the device could evaluate the first (“smallervoltage”) treatment as unsuccessful prior to adjusting treatment (e.g.increasing voltage). Since the evaluation protocol which is selected isdesigned to detect larger tremors, the stimulation protocol with whichit is paired according to S-EV-S set rules, can be designed for thetypes of medical events which will be detected. Analogously, whentreatment signals are generated using control laws, the parameters ofthe control law algorithms can be implemented to realize the principlesof the S-EV-S set rules.

Further, the current invention can use dynamic threshold criteria thatutilize different thresholds according to patient state values (e.g.during different points of the day). A patient may experience the sameamount of tremor, pain, or anxiety as more undesirable in the morningand more tolerable during later parts of the day. If sensed data areused to responsively provide treatment for these symptoms throughout theday using the same threshold criteria then the patient will have tore-adjust the treatment protocol more intermittently then if thethreshold criteria change according to the time of day. Further, in thecurrent invention the sensing protocol can be changed so that differentmeasures of the sensed activity are obtained and evaluated in differentstates. Accordingly, a first set of measures are derived in the “awake”patient state and compared to an independent set of criteria, and asecond set of measures are derived in the “asleep” state and compared toan independent set of criteria, and the first and second set of measuresmay be at least partially independent. This method is unique from simplychanging the threshold criteria, and may be more sensitive to somemedical conditions. It should be reinforced, here and elsewhere insystems according to the invention, that threshold and other criterianeed not be static values or metrics, but may be dynamic and dependenton time, patient state values, and other measures subject to measurementor calculation.

Treatment, Treatment Facilitation, and Symptom Relief.

Known devices deactivate or halt stimulation during sleep, mainly withthe goal of decreasing power usage and habituation effects. While it isnoted that acute cessation of stimulation can lead to unwanted effects,such as the re-emergence of symptoms, this problem is not addressed inknown systems. For example, turning the stimulator off during sleep canpermit elevated symptom levels to return in disorders of pain, anxiety,tremor, or headache and could cause a sleeping patient to awake or maydisrupt normal sleep architecture. In psychiatric disorders, there maybe a lag period between the time that stimulation is initiated and whenthe desired therapeutic benefit is obtained. Due to these concerns it issometimes advantages to decrease or otherwise alter stimulation, ratherthan fully halting it.

In one method of the current invention a parameter of the stimulationprotocol is decreased a relatively large amount in order to decreasepower or drug consumption, while still providing for stimulation whichis sufficient to avoid unwanted effects which would be caused bycomplete cessation of stimulation. When two or more stimulationprotocols are provided, at least one stimulation protocol ischaracterized by a clinically or operationally significant amount, suchas a relative decrease of at least 30% for at least one parameter. Theparameter may relate to voltage level, number of sites at whichstimulation occurs, or duration of stimulation over a given period.

Alternatively, the protocols selected during a particular patient state,such as asleep, may not always utilize less power, but rather, maysimply be oriented towards providing a different type of treatment goalthan in a different state such as the awake state. For example, whilethe awake protocol can address relief from symptoms, the sleep protocolcan be oriented to treating the disorder itself such as increasing aparticular type of neuronal firing that is therapeutic in an indirectmanner. In this case, a first stimulation protocol is used whichdirectly deters or decreases symptoms of a disorder, and a secondstimulation protocol is used which provides a secondary benefit or has asecondary goal. More generally treatment includes providing therapyaccording to a primary treatment goal when the patient is in one stateand a secondary treatment goad when the patient is in a different state.A secondary benefit may be one of the following: a benefit which isindirectly related to the symptoms of the disorder; a benefit whichpromotes neuronal repair of damage caused by the disorder; a benefitwhich is facilitating therapy that will be provided at a later time toprovide symptom relief; a benefit which is to produce a change inneurotransmitter levels in a manner that facilitates subsequent therapyand a benefit which promotes treatment by the first stimulationprotocol. A primary and secondary treatment protocol can be configuredto achieve two different goals, or may be otherwise oriented.

Certain types of stimulation have been shown in scientific literature tomodulate neurotransmitter levels in both near and distal sites fromstimulation, and to assist in neuronal repair. Hence, the secondary typeof stimulation may be directed towards long term treatment by modulatingneurotransmitter levels, or cellular activity, which are related more tothe treatment of the disorder itself rather than to simply providingacute relief of a particular symptom. Because the electrical activity ofthe brain is directly related to its neurochemistry, electricalneuromodulation can alter the biochemical substrates of brain activity,and modulators of this activity, such as neurotransmitter levels,extracellular levels of GABA and glutamate, and ions such as calcium andpotassium (Windels, et al 2003, Graham-Jones et al, 1985). Thesemodulations can, in turn, induce various changes in the membranes of theneurons as well as intracellular processes. Target neuronal tissue canbe more greatly affected by stimulation when the chemicalcharacteristics of the tissue are within certain ranges, including theamount of ions available in the extracellular fluid. The secondarytreatment goals can modify the electrical, metabolic, cellular,molecular or neurochemical profile of brain regions in a manner whichhas a different treatment goal than that of the first protocol.

Certain types of unwanted endogenous activity, such as seizures, firingin a certain manner such as a burst or non-burst mode, firing of certainregions, or types of cells, may only occur when levels of chemicals inthe extracellular fluid, including levels of one or more transmitters,in one or more regions, are within a certain range (e.g., Velisek et al,1994). Rather than responsively stimulating in response to the emergenceof unwanted types of activity, preventive stimulation modulates thesystem in order to decrease the risk that these events will arise in thefuture. Stimulation can occur during patient states such as sleep whichcan deter the levels of transmitters from exceeding the desired rangesduring the subsequent waking state, which, in turn, may cause subsequentneurostimulation oriented towards blocking seizures to be moresuccessful. In one embodiment, a first neurostimulation protocol is usedto produce a desired change in neurochemical levels, and secondneurostimulation protocol is used to provide responsive treatment for adisorder, such as responding to epileptiform activity, and these twoprotocols are selected based upon the state of the patient. In anotherexample, when used to treat a disorder such as gastroparesis, onestimulation protocol can be used during or proximate to food intake tomodulate stomach emptying, while another stimulation protocol is usedperiodically simply to strengthen stomach muscles or provide otherdesired effect. Accordingly, treatment goals can be altered based uponpatient state to achieve a primary treatment goad and a secondarytreatment goal during different states.

Hierarchical Treatment Strategies.

Hierarchical treatment strategies are another feature that may beimplemented by the system according to the invention. Generally,hierarchical treatment strategies can be accomplished in a serialmanner, where the outcomes of lower levels determine whether higherlevel operations occur, and if so which operations these may be. Onetype of hierarchical strategy which has already been discussed is thatuse of patient alerts, where the automatic generation of the alert maybe considered a lower level operation, which then leads to subsequentoperations based upon the patient's response (or lack thereof). In ageneral embodiment; the hierarchical strategy uses lower leveloperations until at least one “level criterion” is satisfied, whichpermits operations at higher levels to occur. Movement from lower tohigher levels can utilize level criteria such as: a threshold criterion;a treatment benefit criterion; a change in patient state; or, thedetection of an event which is not able to be classified with currentsensed data. A number of other multi-stage strategies can provideadvantages as well, some of which will now be described according to thecurrent invention.

Known methods describe utilizing sensed data as may be obtained frommultiple sensors and which may include multiple sensing modalities suchas electrical, optical, and chemical. These different types of data mayall be used to define patient state or to identify an unwanted medicalevent in order to responsively provide treatment. Normally differentmeasures of sensed data can be utilized in combination by applyingunique threshold criteria to each of the measures which are sensed,where if a set of one or more threshold criteria are surpassed then sometype of action occurs. Further, the assessment of different measures maybe combined using a multivariate equation, or using an algorithm havingcompound logical operators such as “and”, “not”, “<”, and others thatwill be apparent to those skilled in the art. These methods allow themultiple measures of sensed data to all contribute to the determinationof patient state or identification of medical event and are examples ofparallel evaluation of sensed data derived from a plurality of sources.

While some advantages of using patient state to adjust the sensing andevaluation protocols have already been discussed, it is an advantage ofthe methods of the current invention to utilize an alternativeembodiment of this method whereby operations and protocols, such assensing protocols, are performed serially in a hierarchical fashion.Serial methods have advantages over methods that assess all informationessentially in parallel, and “hierarchical” analysis of data canespecially provide a number of advantages over the strictly parallelapproach. For example, in the case where multiple sensors are availablein the implanted system, continuous sensing and evaluation from multiplesources will require more memory in the implanted device as well asprocessing resources and will utilize more power. Some sensors requiremore energy than others and this fact should be capitalized on byhierarchical based methods. An EEG amplifier may sense electrical datain a lower level sensing protocol and only when medical events aredetected, and this detection is defined as a level criterion, does anadditional sensor, which may be an optical sensor that may require moreenergy over time, become activated in order to obtain additionalinformation, for example, information related to bloodflow. In anotherinstance, when using neurostimulation to treat a depressed patient, thedetection of theta power in a specific region of the brain may only leadto responsive neuromodulation when levels of serotonin in that area aresimultaneously below a specific level. In a exemplary implementation,serotonin is not sensed, or at least assessed until the theta powerexceeds a level criteria. This is different than a simple combinationcriteria with two operators combined with an “and” condition. In thiscase the second operation does not occur until the first meets a levelcriterion. Accordingly, while neurophysiological measures andneurochemical measures may be combined (e.g. using a model, multivariateequation, or by parallel/sequential logic) in an assessment of aneurological event, the biological (neurological) context within whichcan event occurs, and in determining whether stimulation should occur orbe adjusted; the measures of the second modality are not sensed unlessthere is a chance of the cross-modal measurement (e.g., achemical/electrical ratio utilizing multiplication by constants torelate the two measure in a sensible context) meeting some treatmentcriterion. By sensing according to a first sensing protocol, from afirst subset of sensors, and switching to a second sensing protocol, ofa second subset of sensors according to hierarchical rules the devicecan save power and accomplish adequate sensing with less resources. Forexample, in the case where medical events are not occurring there may beno need to obtain information from, or analyze data from, all availablesensors. Alternatively, if a threshold is exceeded and a medical eventmay be occurring then data from additional sensors can be sensed andanalyzed in order to obtain more information and provide data for whichadditional criteria can be applied.

In addition to sensing, processing and evaluation of sensed data canalso occur using multiple levels, where more extensive analysis occursonly when the analysis from a lower level indicates indicate that thisis necessary. Multi-level operations may also be used for thestimulation protocols, as well as for all treatment operations relatedto a particular protocol or across different types of protocols. Forexample, when the evaluation of sensed data at a lower level indicatethat a medical event has occurred, and stimulation occurs in response tothis event, then afterwards data may be sensed more comprehensively.Just as sensing can occur in a serial manner utilizing a multi-leveldesign, and proceed from lower to higher levels when, for example,threshold criteria are not met, the movement from a lower to a higherlevel can be interleaved with changes to the stimulation and evaluation,protocols.

FIG. 9 shows an embodiment of a multi-level method which can be used tocombine simple and more complex methods of sensing (and evaluation),respectively, in lower and higher stages of an algorithm, and which canbe generalized to a wide number of situations. Although only sensing andevaluation protocols are shown in the figure, stimulation protocols canbe utilized as well or instead. For example, the method can begeneralized to combine the sensing and evaluation a plurality of data ina sequential fashion. Alternatively, the method can use a first type ofprotocol before an event is detected, and different one after an eventis detected. The treatment method can also oscillate between a singleand a multi-level analysis. The alternation between these two types ofanalysis may be made contingent upon the detection of, for example,alert events, patient input, and selected patient states, when these aredefined for level criteria.

In step 230 of FIG. 9, sensed data are obtained according to a firstsensing protocol. The sensed data are related to at least one measure ofthe patient as may be sensed by a particular type (e.g., electrical orchemical) or sensor. According to a first protocol, these data areprocessed 232 and evaluated 234. The evaluation 234 can consist ofprocessing the data to obtain measurements which are compared to a firsttreatment criterion. In step 236 the protocols are selected according tothe evaluation 234 and the next stage of the serial multi-levelalgorithm does not occur 238 a unless a level criterion is met. In step236 if a stimulation protocol dictates that stimulation should occurthen this is done. If the first level criterion is not met 238 a, thenthe algorithm returns to step 230 where and more data are again sensedaccording to a first protocol. If the level criterion is met 236 b thenthe next higher level of the multi-level algorithm occurs. If more dataare required then step 240 occurs where more sensed data are obtainedaccording to a second protocol. This second data set is then alsoanalyzed according to a second protocol which is selected and/oradjusted based upon the first level criterion being met. For example, ifevaluation of the first sensed data (which was achieved by comparingthis data to an epileptiform activity template) indicated that anunwanted medical event was occurring, and caused the first levelcriterion to be met (the first criterion is met because it stipulatesthat this type of activity must occur, although the logic can bearbitrarily switched using a “{tilde over ( )}” logical operation in thecomparison, as is well known), then the second protocol can adjusted orselected based upon characteristics of this failure 238. In this manner,the sensing and evaluation of sensed data 242, 244, (or the stimulationtreatment in an alternative embodiment), can be adjusted to be specificfor the type of event that was detected.

The same signal or data can be iteratively processed using more complexalgorithms, when the algorithms in earlier levels indicate furtherprocessing is needed (e.g. level criteria are met). One example mayinclude a method where EMG tremor only results in stimulation when acardiac or other measure indicates the patient is resting or not engagedin physical activity. The EMG data which is processed to detect muscleactivity, can also be filtered and processed during a second level ofprocessing in order to also measure the patient's EKG and its relatedmeasures such as inter-beat interval. Although the adjustment orselection of any of the protocols of the treatment program can occur atany step of the method according to rules defined in the treatmentprogram, the embodiment shown in FIG. 9, explicitly shows step 238 whichreflects that treatment protocols can be adjusted in a multi-levelmanner to provide serial processing according to results of sensed data,or for other reasons, during the course of treatment. In step 246 if thesecond level criterion is not met 246 a then the process reverts to step230. However if this latter criterion is met as well 246 b, furtherlevels of sensing and evaluation will occur.

The hierarchical method is shown in a simplified embodiment in FIG. 10A,wherein a first treatment protocol is implemented 260, unless afirst-level criterion is met (or exceeded 262 b, depending upon logic offirst-level criterion 262. If the criterion is met 262 b then thetreatment program utilizes a second (higher level) treatment protocol264, otherwise it reverts 262 a to the first treatment protocol 260. Insome instances the implementation of the higher level protocol can occurjointly with the continued operation of the first protocol. While thesecond treatment protocol is active, if a second-level criterion 264 ismet 266 b then the treatment program may utilize a third treatmentprotocol (and so forth, as indicated in the illustration). Otherwise, ifthe second-level criterion is not met 266 a the program will eithercontinue with the second treatment protocol 264 or will return to thefirst treatment protocol 260, depending upon return path rules andcriteria which are assessed in step 268. Return path rules and criteriaare used to allow the treatment program to determine path flow. Forexample, whether certain which steps should be invoked if a levelcriterion is not met. The first treatment protocol 260 can includeautomatically sending out patient alert signals according to an alertprotocol. Calculating the first-level criterion 262 may also utilize analert protocol in order to enable a patient to assist in determining ifcriteria have been met. In FIG. 10A the “(if)” statements indicated thatthe control subsystem may only implement operations if these areindicated by the therapy program.

FIG. 10B extends this approach to a case where a first treatment programprovides therapy in the generalized case, and there are severalfirst-level criteria which can be met in order to cause one of severalsecond-level treatment protocols 264 a, 264 c, 264 d, to be implemented.The different second-level treatment protocols are customizable todetect, evaluate, classify, and adjust and provide treatment accordingto different types of detected medical events or patient state or both.The treatment program can utilize priority rules in order to select anapplicable second-level treatment protocol. For example, if one set ofsecond-level criteria require that conditions A and B are both true,while a different set of second-level criteria require that conditions Aand B and C are all all true, then this latter set of second-levelcriteria might be assigned priority, since it is more specific. In otherwords, level criteria can be constrained by priority rules so that whenmultiple level criteria are met, one level criterion has priority overthe others, so that the subsequent operation occurs according to thispriority. Selection of one or more higher level operations, when usingmultiple level criteria, according to other methods are possible.Additionally, multiple higher level operations can occur simultaneouslywhen multiple level criteria are met.

Two illustrative scenarios in the use of systems and methods accordingto the invention are set forth in FIGS. 11A-11B. Referring now to FIG.11A, an illustrative timeline scenario is presented in which anembodiment of the invention is operative to control therapy deliveryaccording to the time of day and the patient's inputs. For purposes ofthis example, the patient suffers from tremor, and the device 10 a isprogrammed to initiate therapy at a programmed “on time” 1110 of shortlybefore 9:00 a.m. and to end therapy at a programmed “off time” 1112 ofshortly before 9:00 p.m.

On a first day 1114, the patient sleeps 1115 until shortly before theprogrammed “on time” 1110, and accordingly, shortly before theprogrammed “on time” 1110, the device 10 a provides a notice to thepatient (by way of an audio or other alert signal (generated by thedevice 10 a or its programmer 400, for example). To prevent the routinealert signal (i.e., the therapy-on request) from disturbing the patient,a silent alert, such as a blinking light on a patient programmer) may beprovided that will be noticed upon awakening. In the example, becausethe patient is awake, the patient accepts the “activate therapy”operation suggested by the alert signal. For example, the patient canwave a magnet twice over the device 10 a, or can interact with theprogrammer 400 and cause the programmer 400 to communicate theconfirmation to the device 10 a), and therapy is activated 1116according to the patient response rules, at the programmed on time 1110.

Later on the first day 1114, the patient goes back to sleep 1118 at 9:00p.m. Shortly before that time, the device 10 a or programmer 400provides a notice to the patient. Again, the notification may be silentto prevent disturbing the patient if already asleep, but it may bedifferent than (e.g., blink in a different pattern or use a differentcolor) the alert signal which signified the “therapy on” notice. In thiscase, the patient accepts the “therapy off” action prepared by the alertsignal (for example, confirmation can occur by waving the magnet twiceover the device 10 a, or by interacting with the programmer 400), andtherapy turns off 1120. In an embodiment of the invention, the requestto disable therapy for the day may be confirmed also by ignoring thealert, and after a short delay (of, for example 10 seconds to one hour),therapy is turned off according to a priority rule for the “therapy off”event. The alert system may have a patient alert rule which dictatesthat is a patient fails to respond to an alert signal, that a uniquecolor is flashed, for some selected duration, indicating that an alertsignal was “missed” by the patient, and depending upon the flashingpattern, may also indicate that a decision has been made, or operationhas occurred, without the patient's response. The patient can then querythe patient programmer to ascertain what actions have occurred withoutresponse.

On a second day 1122, the patient only sleeps until 6:00 a.m. 1124, andawakes well before therapy is scheduled to initiate 1110 for the day.Accordingly, to enable therapy and provide relief from the patient'ssymptoms, the device 10 a is adapted to receive a patient input (e.g.one or more magnet swipes or an indication made on the programmer 400)to initiate therapy 1126 before the programmed “on time” 1110. Later, atthe programmed “off time” 1112, a “therapy off” alert signal is providedto the patient. Because the patient is watching television 1128 at thattime, the patient rejects the request rather than approving it, andeither inputs a delay value (a specific later time for the therapy toturn off), rejects the operation and requests re-notification at a latertime; or provides a different patient input associated with therejection of the suggested operation, so that the “turn off therapy”operation occurs at a later time 1130.

On a third day 1132, the patient sleeps until 9:00 a.m. 1134, just pastthe programmed on time 1110. Accordingly, no approval is made inresponse to the initial patient alert signal provided by the device 10 aor programmer 400, and therapy is not activated until later 1136, whenthe patient notices the alert and approves the operation suggested bythe “therapy on” alert signal. In a different embodiment, a failure toconfirm a “therapy on” request can result in the request being canceledand the patient must then remember to turn the device on upon awaking.Alternatively, the failure to confirm can lead to an audio signal, whichslowly ramps up in intensity, being added to the visual signal, andother actions may also occur according to the patient alert rules. Laterin the day, the patient turns the therapy off 1138 by manually providingpatient input to the device 10 a or programmer 400. This can cancel a“therapy off” alert signal slated to occur later in the day since thedevice is already in the off state.

It will be noted that in the scenario illustrated in FIG. 11A, twodifferent priority rules are used by the patient alert module, one for“therapy on” and the other for “therapy off.” For therapy on, patientinput prevails over time of day—confirmation is required to turn ontherapy. For therapy off, time of day prevails—failure to confirm stillresults in deactivation. The priority rules here are programmed to varyeither temporally or according to particular alert events.

Referring now to FIG. 11B, an illustrative timeline scenario ispresented in which an embodiment of the invention is operative toactivate and deactivate therapy, control the quantity of therapydelivered, and change responsive detection programs according to thetime of day, elapsed times, patient inputs, detected events, and sensedconditions, using a hierarchical sensing paradigm as described above.Also for this example, the patient suffers from tremor, and the device10 a is programmed to initiate therapy at a programmed “on time” 1210 ofshortly before 9:00 a.m. and to end therapy at a programmed “off time”1212 of shortly before 9:00 p.m.

On a first day 1214, the patient sleeps 1215 until shortly before theprogrammed on time 1210, and while sleeping, an event is detected 1216by the device 10 a. In the example under discussion, therapy is enabledonly for serious medically relevant events, which are defined as beingabove a selected magnitude threshold which is higher than is used whilethe patient is awake, while the patient is sleeping. In this case thedetected event 1216 is below the “sleeping threshold” and does notresult in any therapy being applied. In this case, the patient statevalue has been used to adjust the evaluation protocol.

After the programmed “on time” 1210, when therapy is enabled for alldetected events which are above a lower first threshold, three eventsoccur during the first day 1214 that are sufficient to result in therapybeing applied; a first event 1218, a second event 1220, and a thirdevent 1222. Each detected event is followed by an approximatelyone-hour-long session of therapy. For the first event 1218, the therapyis automatically turned on 1224, therapy is delivered, and therapy islater automatically turned off 1226. Similarly, for the second event1220, therapy is turned on 1228 and later off 1230. However, for thethird event 1222, in the illustrated embodiment, the time betweentherapy on 1232 and therapy off 1234 is shortened by the interveningprogrammed “off” time 1212. This mode of operation may be useful insituations where therapy is disruptive to sleep patterns 1236, and aswith the example set forth in FIG. 11A above, an alert signal may beprovided to the patient, providing the patient with an opportunity toconfirm or reject the premature therapy termination. Such an opportunityto confirm/reject may be made available for any of the mode changes ofoperations performed in a system according to the invention.

On the second day 1238, after awakening from a sleep state 1240, butbefore the programmed on time 1210 passes, a serious event 1242 (majortremor episode) is detected, for example by sensing and analyzing EEF,EMG, or accelerometer signals. Ordinarily, serious events would resultin therapy being applied, even during sleep states, but at this time thepatient is awake, receives an alert from the device 10 a prior totherapy being applied, determines that the detection is a false alarm(based on a high activity level during the exercise session) and cancelsthe therapy 1244. Later that day the patient watches television 1128 andnotices the alert signal and decides that stimulation should occur allnight, the “turn off” therapy operation of the alert signal is rejectedaccording to the patient response, and the patient alert rules dictatethat no further alerts are sent, so that stimulation is not turned offon that particular night and no more alert signals are sent.

On the third day 1246, the patient enables therapy upon awakening fromsleep 1247, and later in the day, an event 1248 is detected, leading totherapy being turned on 1240 (upon patient confirmation of an alertsignal). While therapy is ongoing, a first condition 1252 (for example,a measured increase in susceptibility to tremor) is detected by thedevice 10 a, which has three consequences in the disclosed embodiment:(a) therapy continues, rather than turning off after an interval; (b)the system enables (through either the device 10 a or its programmer400) the patient to increase therapy further, i.e., by requesting anincreased dose; and (c) a second (higher) level of detection, which isordinarily not operative, is enabled to sense further conditions ofdistress.

Before beginning a session of recreation 1253, the patient providesinput 1254 (e.g., a number of magnet swipes over the device 10 a orinteraction with the programmer 400) to increase therapy 1256, asdescribed above. During the recreation, a second condition 1258 isdetected, causing the device 10 a to adjust its therapy settings to adifferent program 1260 as clinically required (the nature of thisprogram may vary from patient to patient, depending on need). Forexample, if the second condition indicates that the previous regimen ofincreased therapy is not effective, a different strategy (e.g.,different waveshape or frequency) may be employed. Based on thedetection of the first condition 1252 and the second condition 1258, a“cumulative” patient alert rule causes therapy to continue after therecreation 1253 ends, although subsequent patient input 1262 lowers themagnitude 1264 of the stimulation of the second therapy program.Further, because of the detection of the first condition 1252 and thesecond condition 1258, therapy continues past the programmed off time1212, until the patient manually deactivates therapy just before goingto sleep 1268. It will be noted that the scenario illustrated in FIG.11B employs a hierarchical sensing strategy as described herein, as thefirst condition 1252 meets level criteria that allows sensing to beginaccording to a (higher) protocol which detects the second condition1258.

The features illustrated in FIGS. 11A-11B and discussed in connectiontherewith are intended to be exemplary and illustrative only, for aparticularly hypothetical patient (which may or may not be reflective ofa real-world clinical scenario) and do not limit the scope of theinvention. Although the example is illustrated with tremor, many othermedical disorders could have been used instead. Various pain disorderscould also be detected by EMG information which reflects abnormal muscletonality of some of those disorders, and other sensors can be used todetect other disorders and symptoms.

External Patient Programmer.

An example of an external patient programmer 400 is shown in FIG. 12 inan embodiment termed “Stimalert”. The programmer 400 is contained in alightweight plastic housing 401 which contains a display screen 408,alert transducers 404 and 406, and control buttons 416 for controllingthe programmer and providing patient input responses. The programmeralso has communication circuitry, for communicating with the imparteddevice and/or a computer (which can run a turnkey software program forcustomizing operation of the programmer and implanted device), which inthis example is achieved via a bluetooth transmitter 402. One of themulti-colored indicators 404 a, can begin to flash hen an alert signaloccurs in the device 10, and is transmitted to the programmer, or isgenerated within the external programmer 400 itself. If the user doesn'trespond within a specified time interval treatment in the device 10 maycontinue according to patient alert rules which may also cause adifferent indicator 404 b to flash and to notify the user of a missedalert signal. The alert signal may also contain an auditory componentwhich is produced by a speaker 406, or the alert signal can be vibratoryand produced by a motor contained within the device 400. The display ofthe programmer 408 can contain a number of display components including:a bar indicator 410 which indicates transmission strength between theimplanted device 10 and the programmer 400; an alert message 410 which,in the example of the figure contains the information about the alertevent, including a proposed operation, a selected delay which will beprovided prior to the initiation of the operation, and the reason thealert was sent; and, a patient response menu 414 which highlights adefault response and waits for the user to confirm this by pressing the“Enter” key 416 a. The user may also change the selected patientresponse using the navigation key 416 b, or can invoke other operationsor modes of the programmer 400 by pressing the “Menu” key 416 c. Thedevice can also contain a number of assignable buttons 416 d-f on theside of the housing 401. The assignable buttons can act as quick-keysfor performing certain functions. In this example, 416 d and 416 e canbe a volume up and volume down adjustment key, respectively, and 416 fcan be a “mute” key which immediately halts an alert signal and alsorejects or accepts the action proposed by different types of alertsignals according to patient alert rules and user preference. Thepatient programmer 400 is configured to work in collaboration with, andmay be conceived as an extension of, the patient alert module 304 of theimplanted device. The programmer 400 can implement various alertoperations by receiving a simple signal from the implanted device 10,such as a code number associated with performing a predefined alertoperation (which is defined in the control subsystem of the externalpatient programmer that is similar to the control subsystem 20 of theimplanted device 10). The programmer 400 can also be configured,according to patient response rules, to automatically send the patient'sinput back to the device at a time when the implanted device isactivated, or can repeat sending the patient's response back until thedevice receives this information and provides a “communication accepted”response. Methods of successfully communicating between an implanteddevice and an external patient programmer are well known, and areimplemented by the programmer which operates to provide the alertsignals according to the methods that have been described herein. Theexternal patient programmer 400 can issue alert signals if it detectsthat it is out of range, low on power, or if it detects any othersituation that will impede its intended function, and which is definedas an alert event.

Further Implementations.

While features of the invention may be especially well suited to be usedin the treatment of brain disorders such as epilepsy, pain, anddepression these can also be used to treat a vast array of medicaldisorders of the brain and body. For example, treatment can be providedfor psychiatric, mood, movement, cognitive and neurological disorders;seizure and epileptiform disorders; pain disorders; depression, anxiety,phobia-related disorders; cardiac, respiratory and metabolic disorders;disorders of syncope; sleeping disorders; migraine; digestion andvoiding disorders, and diabetes. The invention can be particularlybeneficial to pain treatment, since halting therapy at unwanted timescan cause significant discomfort to a patient. Using patient stateinformation the present invention allows automatic, semi-automatic, andmanual adjustment of a protocol prior to, during, or after the time whenthe patient requires the specified treatment. The implanted devices usedin the invention can be, for example, cardiac assist devices includingdefibrillators, cardioverters, mechanical pumps such as a portableembodiment of mechanical ventricular actuation devices (e.g., Biophan'sMYO-VAD) or blood-contacting mechanical pumps (where pumping isunderstood as a type of stimulation treatment), vagal/cranial nervestimulators, and spinal stimulators. The implanted devices can also bedevices which are primarily monitoring devices which may, or may not,work with other implanted devices to provide modulation of a medicaldisorder. The implanted devices can be monitoring devices which are usedto detect unwanted conditions in, for example, the brain or heart. Theimplanted devices can be devices for monitoring activity and providingalarms for such conditions as ischemia, stroke, or epilepsy so that thepatient can seek help. The implanted devices can be cardiac monitoringdevices such as those described in U.S. patent applications 20050165321,and 200050113705, both to Fischell et al. as well as implanted medicalstorage devices for collecting records of cardiac or neurologicalactivity. The implanted devices can also be used in medical treatmentsrelated biological functions rather than disorders such as modulatingprocesses intended to assist or prevent specific conditions related tocontraception, menstruation, weight loss, obesity, and pregnancy.

Treatment for disorders of digestion can include, for example, treatmentof disorders of gastrointestinal motility such as gastroparesis (e.g.,delayed emptying of stomach contents) and gastroesophageal refluxdisease as well as their symptoms (e.g., stomach upset, heartburn,nausea). Electrical stimulation can be used to modulate movement of foodthrough the digestive system and pharmacological stimulation can be usedto, for example, modulate the amounts, strengths, and effects of liquidspresent during direction. Artificial valves, used to treat theredisorders, may also be part of an implanted device that is controlled torealize the features of the present invention where stimulation involvesmodulation of flow. Serotonin receptor agonists, pharmaceuticallyacceptable salts, or a hydrate or solvate thereof, as well as gastricacid suppressing agents can all be used to provide a therapeuticallyeffective amount of therapy, especially when delivered in relation tofood consumption. Stimulation can also be used to therapeuticallymodulate the volume of gastric juice available to reflux, the potency ofthe refluxed material, and the interval that the refluxed materialremains in the esophagus or other area.

Disorders of breathing, which involve disruption of normal respiratorybehaviour, may be a prime candidate for the semi-automatic methodsdescribed herein. Breathing disorders are, for example, central apnea,hypopnea, dyspnea, hyperpnea, tachypnea, and periodic breathing. Apneais a fairly common disorder characterized by periods of interruptedbreathing. Central apnea, is one variant, which causes dysregulation ofbreathing since control signals from the brain to the respiratorymuscles are absent or interrupted. While apnea is popularly known as adisorder which is manifested during sleep, it may also occur while thepatient is awake. However, the protocols which provide benefit to thepatient when awake and asleep are likely to be different and so patientstate is particularly important in this type of application. Theautomatic and semi-automatic adjustment of treatment protocols as hasbeen described herein can include protocols related to activation orde-activation of protocols, and adjustment of protocols related tobreathing based upon patient state, where protocols are selected oradjusted based upon, for example, sleep, wakefulness, and activitylevels, which may be confirmed using patient alerting.

The following material may provide a general understanding for termsused in this specification, while it is also understood that these termscan be modified, adjusted, and altered within other areas ofspecification to achieve alternative embodiments of the invention. Thesedefinitions are provided for illustrative purposes and shall not bedeemed to limit the scope of the invention.

As used herein the terms “stimulation system” or “stimulator” or“device” generally (but not by way of limitation) refer to a system, orpart of a system, that is capable of delivery medical stimulation.Stimulation can include modulating tissue by delivering electrical,optical, magnetic, drug or other therapy. The system is comprised ofcomponents which are either configured in a distributed manner or areprimarily contained within the housing of a single implantable device. Astimulator can be implemented using a generic implantable stimulator ordrug pump such as those manufactured by NeuroPace, Medtronic, Johnson &Johnson, Cyberonics, Guidant, and Advanced Neuromodulation Systems,Inc., which can be configured or adapted to provide electricalstimulation according the principles of the current invention.Accordingly, the stimulator 10, can be realized, for example, as eitheran electrical signal generating stimulator 10 a, or a drug pump 10 b, ora combination of the two.

As used herein, the term “stimulation conduit” may include one or moreleads, each having at least one electrical contact. A stimulationconduit can also be one or more catheters, each of which can be a simplecatheter or a combination catheter/lead capable of providing electricalstimulation or sensing in conjunction with drug delivery. Somestimulators may not include stimulation conduits that travel to distallocations from the housing of the stimulator (e.g. BION™), and in thisinstance the stimulation or sensing probe which resides within or uponthe surface of the stimulator may be used identically during treatment.

As used herein, the term “sensor” can refer to a device for measuring anelectrical, chemical, optical, or other physical property. A sensor mayprovide sensed data relating to multiple characteristics, for example,the flow rate, concentration, and pressure of a fluid. A sensor may bean aggregate of multiple specialized components each configured to sensea different characteristic of the environment in which it is located. Asensor may sense, for example, EEG, EKG, ECG, sound, pressure, strain,temperature, perfusion, optical signals, metabolite levels,neurotransmitter levels, cardiovascular measures such as heart orrespiration rate, glucose level, oxygen saturation level and other typesof information in order to measure state of the patient and toresponsively provide therapy. When possible, the invention can rely uponcompletely implanted sensors, but may also communicate with, externaldevices, or may utilize information derived from assays, or laboratorytechniques, in order to obtain accurate sensed data of the desiredmeasures. In the case of a movement or pain disorder a sensor may be amotion detector or EMG sensor implanted in a limb or can be an EEGsensor located over somatosensory/motor areas of the brain to directlymeasure features of a disorder (e.g., tremor). When used for digestiveor voiding disorders, the sensors can include pressure and strainsensors which gauge the amount of pressure in the bowels, bladder, orany area of the digestive system. The sensor can communicate with andobtain power from the stimulator 10 or can have its own power source maycommunicate via telemetry. A more comprehensive description ofalternative sensor embodiments has previously been made by the inventorin U.S. application Publication No. 20050277912, entitled “Programmablemedical drug delivery systems and methods for delivery of multiplefluids and concentrations”.

As used herein, and not by way of limitation, the term “treatmentprogram” generally refers to a program implemented by the controlsubsystem to provide therapy. The treatment program operates accordingto a treatment protocol. The treatment protocol determines thestimulation, sensing, and evaluation protocols as well as the parametervalues used in these protocols. The treatment program determines, if,how, why, and when the protocols are altered and treatment is provided.The treatment program can be implemented as a software program by thecontrol subsystem, or as specialized hardware within the controlsubsystem 20, for providing control of treatment.

The term “treatment” generally refers at least to operating to providetherapy or performing an action that is medically therapeutic to thepatient. For example, treatment can refer to decreasing or deterring oneor more unwanted symptoms of a disorder, which can be medical events.Treatment can also refer to providing stimulation that decreases thelikelihood of the emergence of unwanted events.

As used herein, “control subsystem” generally refers to a subsystem thatprovides control of the treatment according to a treatment program.

An “operating” is a defined as implementing an algorithm for performingactions according to an embodiment of the invention, which may include(but shall not be limited to) stimulation protocols, detectionprotocols, evaluation protocols.

As used herein “stimulation subsystem” generally refers to a subsystemthat provides stimulation, via at least one stimulation conduit,according to the parameters of a stimulation protocol. The stimulationprotocol determines where, when, and how to stimulate with, for example,one or more types of stimulation. Not only the type of stimulation butalso the number and location of sites at which stimulation can occur aredefined by the stimulation protocols. A stimulation parameter candetermine each characteristic of a stimulation protocol, such as levelof stimulation (e.g., voltage or current), amount of stimulation (e.g.,duration, duration per unit of time), type and site of drug delivery,signal characteristics such as signal shape (or frequency), which ifpulsatile can be pulse shape, duration, or frequency, and numerous othercharacteristics as is known in the art. The stimulation waveform canalso be a sinusoidal or other arbitrary shape. Providing stimulation cancause an increase or decrease in the excitation of target tissue, or maycause another type of desired change. Stimulation can refer modulationof any tissue, fluid, process, or level related to a biological processrelated to the treatment being provided and may include modulation whichis excitatory stimulation, inhibitory stimulation, facilitating ordeterring of a biological condition as desired, and can refer toincreasing the likelihood that biological activity will occur accordingto certain patterns, certain rates, or in selected manners. Thestimulation subsystem can be realized in either a compact module or maybe distributed throughout a system.

As used herein “sensing subsystem” generally refers to a subsystem(either as a single module or distributed throughout a system) thatprovides sensing according to the parameters of a sensing protocol whichdetermines where, when, and how to sense with, for example, one or moreof electrical, optical, or chemical sensors. The sensing protocol can beadjusted, based upon time information or the state of the patient, orboth.

As used herein “evaluation subsystem” refers to a subsystem thatprovides evaluation of the sensed data according to the evaluationprotocol. The evaluation subsystem can compare features of the senseddata after it has been processed to obtain these measurements.Evaluation can entail comparing these measurements using varioustreatment criteria and can include using detection protocols designedfor detecting events such as medical events. The evaluation subsystemcan also compare time information to treatment criteria. The evaluationsubsystem is preferably realized as a module within the controlsubsystem. When sensed data are obtained the control subsystem reliesupon an evaluation protocol to determines if, when and how to evaluatethe sensed data and determines if stimulation occurs in response to thesensed data. The evaluation protocol can be adjusted based upon patientstate, patient responses, level criteria failing to be met and any acombination of these.

As used herein, the term “adjusting” refers to changing or selecting anoperation. Adjusting a protocol may include but shall not be limited toselecting or adjusting a value of a parameter of a protocol or aprotocol that is to be used, generally by a clinically relevant andsignificant amount. Adjustment of the treatment program can include, forexample, changing or selecting stimulation, sensing, or evaluationalgorithm, and can include setting treatment criteria and their values.Adjusting stimulation can include changing the stimulation parameters soas to begin or halt stimulation, and may include the provision ofresponsive stimulation.

As used herein the term “patient state” generally refers to an actual orpredicted state of a patient. Patient state can be derived from timeinformation and/or sensed data information, or patient response datafrom which the state of the patient can be inferred. In addition to timeinformation, sensed data can be data which is sensed and evaluated toprovide a value which is relevant to a patients state (e.g., standing,sitting, sleeping, anxious, experiencing pain) including activity (e.g.,eating), whether or not that state or condition is directly relevant tothe patient's symptoms (e.g. magnitude of tremor).

As used herein “treatment criterion” generally refers to a criterion towhich features of sensed data are compared using the evaluationprotocol. The results of this comparison can be used by the stimulationprogram to determine what type of stimulation takes place; whetherstimulation takes place; and whether treatment is determined to beworking. For example, failure to meed a treatment criterion may causestimulation to occur or may cause a change a different stimulationprotocol to be selected. Alternatively, success in meeting a treatmentcriterion may cause stimulation to be halted or may cause the samestimulation protocol to be selected again. A sensed data treatmentcriterion can be threshold value. A time treatment criterion can be atime value which has been selected to be important to treatment. Forexample, a time value for waking up can be set to cause the treatmentcriterion to be evaluated at true when that time occurs, therebyimplementating an “awake protocol” which is to be used when the patientstate is calculated to be “awake”. A therapy benefit criterion is a typeof treatment criterion. The sensing and evaluation protocols can also bechanged based upon comparisons using treatment criterion.

As used herein, “therapy benefit criterion” generally refers to atreatment criterion which is used to determine if treatment benefit isincreasing, decreasing, or remaining constant, and can be used todetermine the success of treatment. The sensing and evaluation protocolscan also be changed based upon comparisons using treatment criterion.Therapy benefit criteria are treatment criteria which may be values thatcan be compared to sensed activity that is directly related to thedisorder, such as the detection of abnormal medical events. A therapybenefit criterion can be a trend measure of symptom severity measuredover time, where if the trend increases above the therapy benefittreatment criterion then treatment may be evaluated as failing. Thetherapy benefit treatment criterion can be evaluated by the evaluationsubsystem, and will affect operation according to the algorithms of thetreatment program. The evaluation of therapy benefit treatment criteriacan result not only in this criteria being met or not met, but also canresult in scores which determine what to do if the treatment assessed asnot to be working. The scores can be computed using the treatmentbenefit algorithm that is implemented by the evaluation subsystem.

As used herein the term “patient state algorithm” generally describes analgorithm that has “patient state rules” that govern how to define orclassify a patient state. Patient state rules can also define one ormore operations that occur if the patient state is defined in aparticular manner. The patient state algorithm can also adjust the alertprotocol implemented by the patient alert module of the controlsubsystem and can determine what type of alert signals are sent to thepatient.

The term “patient,” when used in connection with user interactionherein, can be used to refer to a patient, a caregiver (particularly ifthe patient is disabled), or a physician using the system. Accordingly,then, the term “patient response” refers to a response provided by apatient, caregiver, or doctor. A patient response can be “no response”if no response is provided within a specified time limit. The term“user” may apply to a patient, caregiver, physician, or other individualinteracting with a system according to the invention.

The term “alert event” refers to any operation or event for whichalerting has been designated to occur.

The term “alert event set” refers to a set of events for which alertsare sent. The alert event set can include: a description of the alertevent; a proposed action that are sent for each of the alert events; atleast one possible proposed operation which may take place for each ofthe alert events; and other relevant information, all of which may bepart of the alert signal which is sent or which can be later accessed bythe patient. Automatically sending an alert and waiting for a responsemay also be referred to as “notification”, and the alert signal is the“notice”.

An “operation” can refer to any action performed by a system accordingto the invention or by a part of such a system, including but notlimited to the performance of algorithms (or portions thereof)implementing stimulation, sensing, evaluation, alerting, detection, andother protocols. “Operating” is performing an operation. “Operatingprotocols” are portions of the treatment program that are used to carryout operations.

An “operating condition” can refer to a detected event, a sensed value,or a data value of a system according to the invention (such as time ofday), satisfying a criterion. The criterion can be defined in an alertevent set such as (but not limited to), can be a treatment criterion,time criterion, a patient state criterion, or a level criterion. An“operating condition” can be satisfied, for example, simply by anoperation occurring or being scheduled to occur, or by a thresholdcriterion being exceeded by a data value.

The contents of all prior art and scientific references cited in thisspecification are hereby incorporated by reference as if recited in fullherein. The embodiments described herein can be altered, adjusted, oramended without departing from the spirit and scope of the invention, asare reflected in the accompanying claims.

SCIENTIFIC REFERENCES

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What is claimed is:
 1. A system for providing therapy to a patientcomprising: an implantable device having a processor configured tocommunicate with an external patient programmer, to monitor the patient,and to provide therapy to the patient; an external patient programmerhaving a processor configured to communicate with the implantablestimulator, to alert the patient, and to receive patient input from thepatient; a processor configured for selectively setting between (1) amanual mode or fully automatic mode and (2) a semi-automatic mode ofoperation, wherein a mode of operation may be selectively and reversiblyswitched between said manual mode, said semi-automatic mode, and saidfully automatic mode of operation; wherein when said either manual modeor fully automatic mode of operation has been selected, operation ofsaid system does not request and await a patient's input, and when saidsemi-automatic mode of operation has been selected, the processor beingfurther configured for: determining whether an adjustment of a therapyprotocol is needed for implementing an adjustment of the therapyprovided by the implantable device by implementing the following stepswhen the adjustment is defined to occur semi-automatically and thedevice is in the semi-automatic mode: proposing the adjustment of thetherapy by sending at least a first alert signal to the patient, saidalert signal being selected from the group consisting of visual signal,auditory signal, vibrotactile signal, or textual signal; delayingimplementation of the adjustment of the therapy protocol for a specifiedtime interval awaiting a patient response; and, operating the processorto implement a patient response rule that is responsive to (a) apredetermined patient response which is provided as patient input, or(b) no patient response provided by the patient within a selectedinterval.
 2. The system of claim 1 wherein the implanted device monitorsthe patient's heart and the adjustment of the therapy protocol includesthe processor being further configured to send alerting signals relatedto patient physiological detected events.
 3. The system of claim 1wherein the implanted device monitors the patient's heart and theadjustment of the therapy protocol within the processor includesproviding of alerting signals related to patient physiological detectedevents.
 4. The system of claim 1 wherein the implanted device monitorsthe patient and the adjustment of the therapy protocol includesoperating a stimulation subsystem to provide electrical stimulation tothe patient.
 5. The system of claim 1 wherein determining whether anadjustment of a therapy protocol is needed includes the detection of analert event.
 6. The system of claim 1 wherein the processor that isconfigured for selectively setting between (1) the manual mode or fullyautomatic mode and (2) the semi-automatic mode of operation is selectedto be the processor of at least one of: the implantable device and theexternal patient programmer.
 7. The system of claim 1 wherein the alertsignal is configured to provide the patient with at least one of: a. anindication of at least one adjustment of the treatment protocol thatwill be made; b. a list of possible adjustments presented in order ofpreference; c. a list of possible adjustments presented in order oflikelihood computed from past patient responses; d. a choice between atleast two adjustments that could be made; e. a question requiring aresponse that is selected from the group consisting of a binary choice,a quantitative value, and a subjective value; and, f. the alert signalto occur at least 1 minute prior to the time that the proposedadjustment is scheduled to occur.
 8. The system of claim 1 whereinprocessor is further configured to refrain from sending a subsequentalert signal to the patient, which proposes the same adjustment as thefirst alert signal, until after a specified delay if the patientresponse to the first alert signal is a “reject” response which rejectsthe proposed adjustment.
 9. The system of claim 1 wherein the patientresponse rule defines a response condition which is evaluated as true ifa specified time interval after said alert signal is sent is exceededwithout the patient providing patient input.
 10. The system of claim 1wherein the processor is further configured to operate to additionallyinclude the step of delaying said implementing of said proposedadjustment of the therapy protocol for a period specified by the patientaccording to the patient response, wherein the patient response is adelay response.
 11. The system of claim 1 wherein determining that anadjustment to the treatment protocol should occur includes detecting analert event using the evaluation of sensed data, wherein the sensed datais at least one of the following types of data: electrical; chemical;optical; hemodynamic; pressure; pO2; pH; temperature; conductivity;impedance; data obtained using mechanical sensors; strain gauge;accelerometer; EEG, EMG, ECG and EKG data; evoked response data; nerveconduction data; data measured from blood; blood glucose concentrationdata; and, data related to diabetes.
 12. The system of claim 1 whereinsaid proposed adjustment of the therapy protocol includes operating atleast one of a set of stimulation and sensing subsystems of theimplanted device to achieve one of: turning off; turning off for aspecified interval; turning on; and, turning on for a specified intervalresponsive to a patient state.
 13. The system of claim 1 wherein thealerting said patient to said proposed adjustment of the therapyprotocol by providing an alert signal further including operating theprocessor to provide an indication that the patient should input a valuefor the proposed adjustment, and receiving this patient input, saidinput being subsequently used when making the adjustment.
 14. The systemof claim 1 wherein the adjustment is for a characteristic of thetreatment which is at least one of: a magnitude of the adjustment; aduration of the adjustment; a rate of transition to the adjustment; and,at least one site at which stimulation occurs for which the adjustmentwill occur.
 15. The system of claim 1 wherein during the automatic modethe patient is alerted to selected operations that occur automaticallyand is not prompted to supply patient input to allow the operations,whereby the patient is notified about an operation that will occurautomatically.
 16. The system of claim 1 wherein during at least thesemi-automatic mode of operation the processor is further configured toallow the patient to manually adjust the treatment protocol in order tomanually cause treatment to occur in a desired manner.
 17. The system ofclaim 1 wherein the processor is further configured within the systemfor selectively setting a manual mode and wherein said system includesan implantable device having a module which is configured to work with apatient programmer to allow the patient to toggle between differentmodes of operation, and wherein the different modes provide fordifferent types of adjustment of the operation of the system, the modesincluding at least two of: said fully automatic mode, saidsemi-automatic mode, and said manual mode.
 18. The system of claim 1wherein selective setting of mode occurs according to user inputreflecting the patient's preference and wherein the inputs selects foronly one mode to be active.
 19. The system of claim 1 wherein selectivesetting of mode occurs at different times according to patient state.20. The system of claim 1 wherein a processor within the system isfurther configured for selective setting of mode which causes aparticular adjustment of the treatment to occur according to a protocolthat is defined to occur at least one of a semi-automatically, fullyautomatically, or manually depending upon whether the selected mode issemi-automatic, fully automatic or manual.
 21. The system of claim 1wherein selective setting of mode is selected contingently upon whetherthe patient state indicates the patient is either awake or sleeping.